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  • 1. Bostanci, Nagihan
    et al.
    Ramberg, Per
    Wahlander, Åsa
    Grossman, Jonas
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Barnes, Virginia Monsul
    Papapanou, Panos
    Label-free quantitative proteomics reveals differentially regulated proteins in experimental gingivitis2013In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 2, no 12, p. 657-678Article in journal (Refereed)
    Abstract [en]

    We investigated the sequential protein expression in gingival crevicular fluid samples during the induction (I) and resolution (R) of experimental gingivitis. Periodontally and systemically healthy volunteers (n = 20) participated in a three-week experimental gingivitis protocol, followed by debridement and two weeks of regular plaque control. Gingival crevicular fluid (GCF) samples were collected at baseline, Day 7, 14, and 21 (induction; I-phase), and at Day 21, 25, 30, and 35 (resolution; R-phase). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for label-free quantitative proteomics was applied. A total of 287 proteins were identified including 254 human, 14 bacterial, 12 fungal, and 7 yeast proteins. Ontology analysis revealed proteins primarily involved in cytoskeletal rearrangements, immune response, antimicrobial function, protein degradation, and DNA binding. There was considerable variation in the number of proteins identified, both among subjects and within subjects across time points. After pooling of samples between subjects at each time point, the levels of 59 proteins in the I-phase and 73 proteins in the R-phase were quantified longitudinally. Our data demonstrate that LC-MS/MS label-free quantitative proteomics is valuable in the assessment of the protein content of the GCF and can facilitate a better understanding of the molecular mechanisms involved in the induction and resolution of plaque-induced gingival inflammation in humans.

  • 2.
    Brunkwall, Louise
    et al.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ericson, Ulrika
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Hellstrand, Sophie
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Kennbäck, Cecilia
    Department of Internal Medicine, Skane University Hospital, Jan Waldenströms gata 15, 5th floor, 20502, Malmö, Sweden.
    Östling, Gerd
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Jujic, Amra
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Cardiology, Skane University Hospital, Malmö, Sweden.
    Melander, Olle
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skane University Hospital, Jan Waldenströms gata 15, 5th floor, 20502, Malmö, Sweden.
    Engström, Gunnar
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Nilsson, Jan
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Cardiology, Skane University Hospital, Malmö, Sweden.
    Ohlsson, Bodil
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skane University Hospital, Jan Waldenströms gata 15, 5th floor, 20502, Malmö, Sweden.
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD).
    Orho-Melander, Marju
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Persson, Margaretha
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skane University Hospital, Jan Waldenströms gata 15, 5th floor, 20502, Malmö, Sweden.
    Nilsson, Peter M
    Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skane University Hospital, Jan Waldenströms gata 15, 5th floor, 20502, Malmö.
    The Malmö Offspring Study (MOS): design, methods and first results.2021In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 36, p. 103-116Article in journal (Refereed)
    Abstract [en]

    As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

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  • 3.
    De Silva, Kushan
    et al.
    Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia..
    Demmer, Ryan T.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.;Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA..
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Lund Univ, Dept Clin Sci, S-21428 Malmo, Sweden.
    Mousa, Aya
    Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia..
    Forbes, Andrew
    Monash Univ, Fac Med Nursing & Hlth Sci, Sch Publ Hlth & Prevent Med, Biostat Unit,Div Res Methodol, Melbourne, Vic 3004, Australia..
    Enticott, Joanne
    Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia..
    Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: a bioinformatics analytic workflow2022In: Functional & Integrative Genomics, ISSN 1438-793X, E-ISSN 1438-7948, Vol. 22, p. 1003-1029Article in journal (Refereed)
    Abstract [en]

    Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.

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  • 4. De Silva, Kushan
    et al.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD).
    Demmer, Ryan T
    A combined strategy of feature selection and machine learning to identify predictors of prediabetes2020In: JAMIA Journal of the American Medical Informatics Association, ISSN 1067-5027, E-ISSN 1527-974X, Vol. 27, no 3, p. 396-406Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify predictors of prediabetes using feature selection and machine learning on a nationally representative sample of the US population.

    MATERIALS AND METHODS: We analyzed n = 6346 men and women enrolled in the National Health and Nutrition Examination Survey 2013-2014. Prediabetes was defined using American Diabetes Association guidelines. The sample was randomly partitioned to training (n = 3174) and internal validation (n = 3172) sets. Feature selection algorithms were run on training data containing 156 preselected exposure variables. Four machine learning algorithms were applied on 46 exposure variables in original and resampled training datasets built using 4 resampling methods. Predictive models were tested on internal validation data (n = 3172) and external validation data (n = 3000) prepared from National Health and Nutrition Examination Survey 2011-2012. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). Predictors were assessed by odds ratios in logistic models and variable importance in others. The Centers for Disease Control (CDC) prediabetes screening tool was the benchmark to compare model performance.

    RESULTS: Prediabetes prevalence was 23.43%. The CDC prediabetes screening tool produced 64.40% AUROC. Seven optimal (≥ 70% AUROC) models identified 25 predictors including 4 potentially novel associations; 20 by both logistic and other nonlinear/ensemble models and 5 solely by the latter. All optimal models outperformed the CDC prediabetes screening tool (P < 0.05).

    DISCUSSION: Combined use of feature selection and machine learning increased predictive performance outperforming the recommended screening tool. A range of predictors of prediabetes was identified.

    CONCLUSION: This work demonstrated the value of combining feature selection with machine learning to identify a wide range of predictors that could enhance prediabetes prediction and clinical decision-making.

  • 5.
    De Silva, Kushan
    et al.
    Monash University, Clayton, Australia.
    Lim, Siew
    Monash University, Clayton, Australia.
    Mousa, Aya
    Monash University, Clayton, Australia.
    Teede, Helena
    Monash University, Clayton, Australia.
    Forbes, Andrew
    Monash University, Clayton, Australia.
    Demmer, Ryan T
    University of Minnesota, Minneapolis, Minnesota, United States of America; Columbia University, New York, New York, United States of America.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD).
    Enticott, Joanne
    Monash University, Clayton, Australia.
    Nutritional markers of undiagnosed type 2 diabetes in adults: Findings of a machine learning analysis with external validation and benchmarking.2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 5, article id e0250832Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Using a nationally-representative, cross-sectional cohort, we examined nutritional markers of undiagnosed type 2 diabetes in adults via machine learning.

    METHODS: A total of 16429 men and non-pregnant women ≥ 20 years of age were analysed from five consecutive cycles of the National Health and Nutrition Examination Survey. Cohorts from years 2013-2016 (n = 6673) was used for external validation. Undiagnosed type 2 diabetes was determined by a negative response to the question "Have you ever been told by a doctor that you have diabetes?" and a positive glycaemic response to one or more of the three diagnostic tests (HbA1c > 6.4% or FPG >125 mg/dl or 2-hr post-OGTT glucose > 200mg/dl). Following comprehensive literature search, 114 potential nutritional markers were modelled with 13 behavioural and 12 socio-economic variables. We tested three machine learning algorithms on original and resampled training datasets built using three resampling methods. From this, the derived 12 predictive models were validated on internal- and external validation cohorts. Magnitudes of associations were gauged through odds ratios in logistic models and variable importance in others. Models were benchmarked against the ADA diabetes risk test.

    RESULTS: The prevalence of undiagnosed type 2 diabetes was 5.26%. Four best-performing models (AUROC range: 74.9%-75.7%) classified 39 markers of undiagnosed type 2 diabetes; 28 via one or more of the three best-performing non-linear/ensemble models and 11 uniquely by the logistic model. They comprised 14 nutrient-based, 12 anthropometry-based, 9 socio-behavioural, and 4 diet-associated markers. AUROC of all models were on a par with ADA diabetes risk test on both internal and external validation cohorts (p>0.05).

    CONCLUSIONS: Models performed comparably to the chosen benchmark. Novel behavioural markers such as the number of meals not prepared from home were revealed. This approach may be useful in nutritional epidemiology to unravel new associations with type 2 diabetes.

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  • 6.
    De Silva, Kushan
    et al.
    Monash University, Australia.
    Mathews, Noel
    Monash University, Australia.
    Teede, Helena
    Monash University, Australia.
    Forbes, Andrew
    Monash University, Australia.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Swedish Dental Service of Skane.
    Demmer, Ryan T.
    University of Minnesota, USA; Columbia University, USA.
    Enticott, Joanne
    Monash University, Australia.
    Clinical notes as prognostic markers of mortality associated with diabetes mellitus following critical care: A retrospective cohort analysis using machine learning and unstructured big data2021In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 132, article id 104305Article in journal (Refereed)
    Abstract [en]

    Background: Clinical notes are ubiquitous resources offering potential value in optimizing critical care via data mining technologies. Objective: To determine the predictive value of clinical notes as prognostic markers of 1-year all-cause mortality among people with diabetes following critical care. Materials and methods: Mortality of diabetes patients were predicted using three cohorts of clinical text in a critical care database, written by physicians (n = 45253), nurses (159027), and both (n = 204280). Natural language processing was used to pre-process text documents and LASSO-regularized logistic regression models were trained and tested. Confusion matrix metrics of each model were calculated and AUROC estimates between models were compared. All predictive words and corresponding coefficients were extracted. Outcome probability associated with each text document was estimated. Results: Models built on clinical text of physicians, nurses, and the combined cohort predicted mortality with AUROC of 0.996, 0.893, and 0.922, respectively. Predictive performance of the models significantly differed from one another whereas inter-rater reliability ranged from substantial to almost perfect across them. Number of predictive words with non-zero coefficients were 3994, 8159, and 10579, respectively, in the models of physicians, nurses, and the combined cohort. Physicians & rsquo; and nursing notes, both individually and when combined, strongly predicted 1-year all-cause mortality among people with diabetes following critical care. Conclusion: Clinical notes of physicians and nurses are strong and novel prognostic markers of diabetes-associated mortality in critical care, offering potentially generalizable and scalable applications. Clinical text-derived personalized risk estimates of prognostic outcomes such as mortality could be used to optimize patient care.

  • 7.
    Divaris, K
    et al.
    Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Haworth, S
    Medical Research Council Integrative Epidemiology United, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Bristol Dental School, University of Bristol, Bristol, UK.
    Shaffer, J R
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
    Anttonen, V
    Research Unit of Oral Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
    Beck, J D
    Division of Comprehensive Oral Health-Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Furuichi, Y
    Division of Endodontology and Periodontology, Department of Oral Rehabilitation, Graduate School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan.
    Holtfreter, B
    Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Public Dental Service of Skåne, Lund, Sweden; Hypertension and Cardiovascular Disease, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
    Kocher, T
    Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
    Levy, S M
    Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Iowa City, IA, USA.
    Magnusson, P K E
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    McNeil, D W
    Center for Oral Health Research in Appalachia, Appalachia, NY, USA; Department of Psychology, West Virginia University, Morgantown, WV, USA; Department of Dental Public Health & Professional Practice, West Virginia University, Morgantown, WV, USA.
    Michaëlsson, K
    Department of Surgical Sciences, Unit of Medical Epidemiology, Uppsala University, Uppsala, Sweden.
    North, K E
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Palotie, U
    Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Papapanou, P N
    Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University, College of Dental Medicine, New York, NY, USA.
    Pussinen, P J
    Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; nstitute of Dentistry, School on Medicine, University of Eastern Finland, Kuopio, Finland.
    Porteous, D
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
    Reis, K
    Institute of Genomics, University of Tartu, Tartu, Estonia.
    Salminen, A
    Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Schaefer, A S
    Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité-Universitätsmedizin Berlin, Berlin, Germany.
    Sudo, T
    Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan.
    Sun, Y Q
    Center for Oral Health Services and Research Mid-Norway (TkMidt), Trondheim, Norway; Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
    Suominen, A L
    Institute of Dentistry, School on Medicine, University of Eastern Finland, Kuopio, Finland; Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland; Public Health Evaluation and Projection Unit, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
    Tamahara, T
    Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
    Weinberg, S M
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
    Lundberg, P
    Department of Odontology, Section of Molecular Periodontology, Umeå University, Umeå, Sweden.
    Marazita, M L
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
    Johansson, I
    Department of Odontology, Section of Cariology, Umeå University, Umeå, Sweden.
    Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.2022In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 101, no 11, p. 1408-1416, article id 220345221109775Article in journal (Refereed)
    Abstract [en]

    Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

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  • 8. Dommisch, Henrik
    et al.
    Kuzmanova, Denica
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD).
    Grant, Melissa
    Chapple, Iain
    Effect of micronutrient malnutrition on periodontal disease and periodontal therapy2018In: Periodontology 2000, ISSN 0906-6713, E-ISSN 1600-0757, Vol. 78, no 1, p. 129-153Article, review/survey (Refereed)
    Abstract [en]

    Periodontitis is a complex chronic inflammatory noncommunicable disease, initiated by the development of a dysbiotic microbial plaque biofilm below the gingival margin. Whilst the pathogenic biofilm is a “necessary cause” of periodontitis, it is insufficient on its own to cause the disease, and a destructive immune‐inflammatory response is a key to the translation of risk to destructive events. Other exposures or “component causes” include individual genetic predisposition, lifestyle (including smoking and nutrition), and environmental factors. Dietary nutrients are essential for life as they provide crucial energy sources in the form of macronutrients, as well as important cofactors in the form of micronutrients, which regulate the functionality of enzymes during the regulation of anabolic and catabolic processes in human cells. Moreover, micronutrients can regulate gene transcription factors, such as the proinflammatory nuclear factor kappa B and the anti‐inflammatory nuclear factor (erythroid‐derived 2)‐like 2. This review focuses on the role of vitamins (vitamin A, carotenoids, the vitamin B complex, vitamins C, D, and E, and coenzyme Q10) and minerals (calcium, magnesium, iron, zinc, potassium, copper, manganese, and selenium) in human physiology and the impact of their deficiencies upon periodontal health and disease.

  • 9.
    Grant, Melissa
    et al.
    School of Dentistry, Institute of Clinical Sciences, University of Birmingham and Birmingham Community Healthcare Foundation Trust, Birmingham, United Kingdom.
    Kilsgård, Ola
    Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Åkerman, Sigvard
    Malmö University, Faculty of Odontology (OD). Swedish Dental Service of Skåne, Lund, Sweden.
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD). Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Solna, Sweden.
    Demmer, Ryan T
    Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
    Malmström, Johan
    Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Swedish Dental Service of Skåne, Lund, Sweden.
    The Human Salivary Antimicrobial Peptide Profile according to the Oral Microbiota in Health, Periodontitis and Smoking.2019In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 11, no 5, p. 432-443Article in journal (Refereed)
    Abstract [en]

    Antimicrobial peptides (AMPs) are a diverse family of peptides that defend the mucosal surfaces of the oral cavity and other locations. Many AMPs have multiple functions and properties that influence aspects of innate defense and colonization by microorganisms. The human oral cavity is home to the second-most diverse microbiome, and the health of the mouth is influenced by the presence of these bacteria as well as by extrinsic factors such as periodontitis and smoking. This study hypothesized that the AMP profile is different in the presence of extrinsic factors and that this would also be reflected in the bacteria present. The AMP profile was analyzed by quantitative selected-reaction-monitoring mass spectrometry analysis and 40 bacterial species were quantified by DNA-DNA hybridization in saliva donated by 41 individuals. Periodontal status was assessed through dental examination and smoking status through medical charting. Periodontal health (in nonsmokers) was associated with a higher abundance of ribonuclease 7, protachykinin 1, β-defensin 128, lipocalin 1, bactericidal permeability-increasing protein fold-containing family B member 3, and bone-marrow proteoglycan. Nonsmoking periodontal disease was associated with an abundance of neutrophil defensin 1 and cathelicidin. However, 7 AMPs were overabundant in periodontal disease in smokers: adrenomedullin, eosinophil peroxidase, 3 different histones, myeloperoxidase, and neutrophil defensin 1. There were no differentially abundant AMPs in smokers versus nonsmokers with periodontal health. Correlation network inference of healthy nonsmokers, healthy smokers, nonsmoking periodontitis, or smoking periodontitis donors demonstrated very different networks growing in complexity with increasing numbers of stressors. The study highlights the importance of the interaction between the oral cavity and its resident microbiota and how this may be influenced by periodontal disease and smoking.

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  • 10.
    Grant, Melissa M
    et al.
    School of Dentistry, Institute of Clinical Sciences, University of Birmingham and Birmingham Community Healthcare Foundation Trust, Birmingham B5 7EG, UK.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Swedish Dental Service of Skåne, 222 37 Lund, Sweden.
    Next Generation Sequencing Discoveries of the Nitrate-Responsive Oral Microbiome and Its Effect on Vascular Responses2019In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 8, no 8, article id 1110Article in journal (Refereed)
    Abstract [en]

    Cardiovascular disease is a worldwide human condition which has multiple underlying contributing factors: one of these is long-term increased blood pressure-hypertension. Nitric oxide (NO) is a small nitrogenous radical species that has a number of physiological functions including vasodilation. It can be produced enzymatically through host nitric oxide synthases and by an alternative nitrate-nitrite-NO pathway from ingested inorganic nitrate. It was discovered that this route relies on the ability of the oral microbiota to reduce nitrate to nitrite and NO. Next generation sequencing has been used over the past two decades to gain deeper insight into the microbes involved, their location and the effect of their removal from the oral cavity. This review article presents this research and comments briefly on future directions.

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    FULLTEXT01
  • 11.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Antimicrobial Peptides: Roles in Periodontal Health and Disease2017In: Pathogenesis of Periodontal Diseases: Biological Concepts for Clinicians / [ed] Nagihan Bostanci; Georgios N. Belibasakis, Springer, 2017, p. 97-110Chapter in book (Refereed)
    Abstract [en]

    Why do cockroaches and rats survive in sewers and other extremely challenging conditions? The answer is that through evolution they have been equipped with antimicrobial peptides (AMPs) that protect them from microbiological insult. In the case of cockroaches and rats, the AMPs are very potent, allowing for these challenging environments [1–3]. AMPs are the most ancient and primitive arm of the human immune system and are expressed in mammals, insects, fungus, trees—virtually every multicellular organism that coexist with bacteria, including bacteria. AMPs cover the outer barriers of our body, such as epithelium and skin, enabling us to live in coexistence with what some consider a complex organ—the microbiome [4]. As we now, through the technological advancements in microbiology, start to comprehend the complexity of the microbiome, we can also appreciate the complexity of the AMP-profile. 

  • 12. Jönsson, Daniel
    Effects of bacterial lipopolysaccharide and estrogen on human periodontal ligament cell properties2007Manuscript (preprint) (Other academic)
  • 13.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Fynd kan leda till skräddarsydda preparat2007In: Tandläkartidningen, ISSN 0039-6982, no 12, p. 56-59Article in journal (Other academic)
    Abstract [sv]

    Med anledning av avhandlingen The biological role of the female sex hormone estrogen in the periodontium : studies on human periodontal ligament cells. Framtida hormonersättningspreparat kommer sannolikt att designas efter den enskilda individens behov. Kunskaper om hur dessa preparat påverkar parodontiet kommer därför att få stor betydelse. Studien har lett till grundläggande kunskaper om hur östrogen påverkar celler på proteinnivå.

  • 14.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    The Biological Role of the Female Sex Hormone Estrogen in the Periodontium2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Several studies have addressed the association between changes in levels of the female sex hormone, estrogen, and changes in the parameters of periodontitis, but the mechanism behind estrogeniceffects in the periodontium is poorly understood. There are two subtypes of estrogen receptors (ER), ERα and ERβ. The objectives of the present studies were to map periodontal ligament (PDL) cell ERsubtypeexpression patterns and to investigate their functional importance. This information is valuable for understanding the biologicalrole of ERs in the periodontium.Methods: Human PDL cells were obtained from periodontal tissue explants from teeth that were extracted for orthodontic reasons. Theprogesterone receptor and ER-subtype expression patterns were studied using immunocytochemistry. The subcellular distribution of ERβ was determined by immunogold electron microscopy and confocalimaging using the mitochondria-selective probe MitoTracker® and ERβ immunostaining. Expression of the mitochondrial protein, cytochrome c oxidase subunit I, was investigated using Western blotting. DNA and collagen synthesis was determined by measuring the incorporation of [3H]thymidine and [3H]proline, respectively. Interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP) were analyzed using ELISA. Alkaline phosphataseactivity was determined colorimetrically.Results and Discussion: Human PDL cells possessed immunoreactivity for ERβ but not ERα, suggesting that estrogenic effects in PDL cells are mediated via ERβ. PDL cells expressed no immunoreactivity for progesterone receptors, which implies that progesterone does not have a direct effect on PDL cell function. Confocal imaging and immunogold electron microscopy revealed that ERβ immunoreactivity was distributed not only in the nucleus but also in the mitochondria. Incubation with estrogen down-regulated expression of cytochrome coxidase subunit I, indicating functional significance for mitochondrial ER. Physiological concentrations of estrogen had no effect on PDL cell collagen and DNA synthesis but enhanced DNA synthesisin human breast cancer MCF-7 cells, probably reflecting a cell-typespecific ER-subtype expression pattern. The bacterial endotoxin,LPS, had no effect on the physiological properties of PDL cells (demonstratedby alkaline phosphatase activity, and DNA and collagen synthesis). However, LPS enhanced inflammatory characteristics ofPDL cells, such as enhanced IL-6 and MCP-1 protein production. The LPS-induced effect on PDL cells was not reversed by estrogen,suggesting that estrogen has no anti-inflammatory effect via this mechanism. The enhanced MCP-1 expression in response to LPS suggests that PDL cells contribute to the recruitment of leukocytes in periodontal inflammation.

  • 15.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Tissue senescence and periodontal disease: A reciprocal association?2013In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 7, no 58, p. 753-754Article in journal (Other academic)
  • 16.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Aggarwal, Prerna
    Nilsson, Bengt-Olof
    Demmer, Ryan
    Beneficial effects of hormone replacement therapy on periodontitis are vitamin D associated2013In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 8, no 84, p. 1048-1057Article in journal (Refereed)
    Abstract [en]

    Background: Possible synergism between female sex hormones and vitamin D on periodontitis pathology has not been assessed. Here, the authors investigate effects of estrogen, progesterone, and vitamin D on periodontitis in a population-based sample and use cell studies to explore mechanistic explanations of the population-based findings. Methods: The epidemiologic analysis uses cross-sectional data from the continuous National Health and Nutrition Examination Survey 2001 to 2004. The cross sections include 1,230 women aged 40 to 85 years who received a periodontal examination, responded to questions regarding hormone replacement therapy (HRT), and provided a blood sample for serum vitamin D assessments. For mechanistic cell culture studies, human monocytes were cultured with or without lipopolysaccharide (LPS), estradiol, progesterone, and/or 1,25-dihydroxyvitamin D3; and transcriptional activity of interleukin (IL)-6, IL-1β, B lymphocyte chemoattractant (BLC), and regulated on activation normal T-cell expressed and secreted (RANTES) was assessed. Results: HRT use (versus none) was associated with higher attachment levels and more teeth only among participants who were vitamin D sufficient (>20 ng/mL). The odds ratio for having moderate/severe periodontitis among users of HRT versus participants who did not use HRT was 0.69 among participants who were vitamin D sufficient and 1.19 in participants who were vitamin D deficient. LPS-induced IL-6, IL-1β, and BLC expression was attenuated in human monocytes treated with estrogen and progesterone. Downregulation of IL-6 expression by estrogen and progesterone was potentiated when vitamin D was included. LPS-induced IL-6 and RANTES expression was decreased, and BLC expression was totally reversed, by vitamin D treatment. Conclusions: The association between HRT and clinical periodontal measures was strongest among women with high vitamin D levels. This association is plausibly mediated via an anti-inflammatory transcriptional mechanism.

  • 17.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Amisten, Stefan
    Bratthall, Gunilla
    Holm, Anders
    Nilsson, Bengt-Olof
    LPS induces GROα chemokine production via NFκB in oral fibroblasts2009In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 11, no 58, p. 791-796Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE AND DESIGN: Chemotaxis of neutrophils from blood to the inflammation process plays an important role in development of periodontal inflammation. The novel chemokine GROalpha, also named CXCL1, is a strong chemoattractant for neutrophils. Data on production and regulation of GROalpha by oral fibroblasts have not previously been presented. MATERIALS AND METHODS: GROalpha mRNA and protein levels were determined in human periodontal ligament cells and mouse gingival fibroblasts by quantitative real-time PCR and ELISA. RESULTS: We disclose that both human periodontal ligament cells and mouse gingival fibroblasts produce GROalpha in response to LPS stimulation. Stimulation with LPS for 24 h increased both mRNA for GROalpha and GROalpha protein. The steroid hormone estrogen had no effect on LPS-induced GROalpha mRNA expression. Treatment with the glucocorticoid dexamethasone attenuated LPS-induced GROalpha production, and the NF-kappaB blocker MG 132 fully prevented LPS-induced GROalpha. CONCLUSIONS: Oral fibroblasts respond to LPS stimulation by increasing GROalpha production via the transcription factor NF-kappaB, suggesting that this mechanism may be involved in development of periodontal inflammation.

  • 18.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Andersson, Gunilla
    Malmö högskola, Faculty of Odontology (OD).
    Ekblad, Eva
    Liang, Min
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Immunocytochemical Demonstration of Estrogen Receptor Beta in Human Periodontal Ligament Cells2004In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 49, no 1, p. 85-88Article in journal (Refereed)
    Abstract [en]

    Two transcription associated estrogen receptor (ER) subtypes have been identified and named ERalpha and ERbeta. In the present study we investigate the expression of these ER subtypes in cultured human periodontal ligament (PDL) cells by immunocytochemistry. ERbeta immunoreactivity was observed in the nuclei of about 40% of the PDL cells, while no ERalpha immunoreactivity was detected. In human breast cancer MCF-7 cells, serving as positive controls, both ERalpha and ERbeta immunoreactivities were demonstrated. No immunoreactivity was observed after omission of the primary antibodies. This study suggests that estrogen acts on gene transcription preferentially via ERbeta in human PDL cells.

  • 19.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Functional effects of estrogen in the periodontium2007Conference paper (Refereed)
    Abstract [en]

    Objectives: Several studies have addressed the association between changes in the female sex hormones estrogen and progesterone levels and changes in parameters of periodontitis. We have previously shown that periodontal ligament cells (PDL cells) express estrogen receptor β (ERβ) but not ERα immunoreactivity. The PDL cells express no immunoreactivity for progesterone receptors, suggesting that this cell-type is not affected by progesterone. Treatment with a physiological concentration of estrogen increases DNA synthesis in human breast cancer cells but has no effect on PDL cell DNA and collagen synthesis. The purpose of this project is to investigate the mechanisms by which estrogen influences structure and function of the periodontal ligament by affecting PDL cell functional properties. Methods: Human PDL cells were obtained from teeth extracted for orthodontic reasons. The cells were cultured from periodontal tissue explants and used in passages 3-5. Subcellular distribution of ERβ was determined by immunogold electron microscopy and confocal imagining using the mitochondrial selective probe MitoTracker and ERβ immunostaining. Expression of mitochondrial protein cytochrome c oxidase subunit I was investigated using Western blotting. The amount of IL-6 was determined by ELISA. Results: Confocal imaging revealed that ERβ immunoreactivity was distributed not only in the nucleus but also in the mitochondria. These results were confirmed using immunogold electron microscopy. Incubation with estrogen down-regulated the mitochondrial enzyme cytochrome c oxidase subunit I expression by about 30%, showing functional significance of mitochondrial ER. Preliminary data show that estrogen attenuates LPS induced IL-6 production in the PDL cells. Conclusion: Our data show that estrogen, preferably via ERβ, affects PDL cell functional properties, suggesting that estrogen and other ER specific ligands may modulate the periodontal tissue structure and function in health and disease.

  • 20.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Functional effects of female sex hormones in the periodontium2006Conference paper (Other academic)
    Abstract [en]

    Aim: Several studies have addressed the association between changes in the female sex hormones estrogen and progesterone levels and changes in parameters of periodontitis. In order to understand how these hormones affect periodontal health it is of major importance to obtain information on their physiological importance. We have previously shown that periodontal ligament cells (PDL cells) express estrogen receptor beta (ER beta) but not ER alfa immunoreactivity. The PDL cells express no immunoreactivity for progesterone receptors, suggesting that this cell type is not affected by progesterone. Treatment with a physiological concentration (100 nM) of estrogen increases DNA synthesis in human breast cancer cells but has no effect on PDL cell DNA and collagen synthesis. The purpose of this project is to investigate how and by which mechanisms estrogen influences structure and function of the periodontal ligament by affecting PDL cell functional properties. Methods: Human PDL cells were obtained from teeth extracted for orthodontic reasons. The cells were cultured from periodontal tissue explants and used in passages 3-5. Subcellular distribution of ER beta was determined by immunogold electron microscopy and confocal imagining using the mitochondrial selective probe MitoTracker and ER beta immunostaining. Expression of mitochondrial protein cytochrome c oxidase subunit I was investigated using Western blotting. The amounts of IL-6 and c-reactive protein (CRP) were determined by ELISA. Results: Confocal imaging revealed that ER beta immunoreactivity was distributed not only in the nucleus but also in the mitochondria. These results were confirmed using immunogold electron microscopy. Incubation with estrogen down-regulated the mitochondrial enzyme cytochrome c oxidase subunit I expression by about 30%, showing functional significance of mitochondrial ER. Preliminary data show that lipopolysaccharide (LPS) induces IL-6 but not CRP expression in PDL cells. The LPS induced IL-6 production is not affected by estrogen. Conclusion: Our data show that estrogen, preferably via ER beta, affects PDL cell functional properties, suggesting that estrogen and other ER specific ligands may modulate the periodontal tissue structure and function in health and disease.

  • 21.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Functional effects of LPS and estrogen in the periodontium2007Conference paper (Refereed)
    Abstract [en]

    Objectives: Several studies have addressed the association between changes in the female sex hormones estrogen levels and changes in parameters of periodontitis. Estrogen affects inflammatory conditions in different parts of the body, such as brain, cardiovascular system and in colon. The effects of LPS in PDL cell inflammatory versus normal physiological conditions are poorly mapped. The aim of the present study was to investigate how LPS affects PDL cell inflammatory versus normal physiological characteristics, and if the effect of LPS was reversed by estrogen. Methods: Human PDL cells were obtained from teeth extracted for orthodontic reasons. The cells were cultured from periodontal tissue explants and used in passages 3-5. The cells were treated with different concentrations of Escherichia coli LPS in the absence or presence of estrogen. Cytokine (IL-6 and CRP) and chemokine (MCP-1) production was measured using ELISA. DNA and collagen synthesis was determined by measuring the incorporation of [3H]thymidine and [3H]proline, respectively. ALP activity was determined colorimetrically. All measurements were normalized to total amount of protein. Results and Conclusions: LPS enhanced the inflammatory characteristics of PDL cells, reflected by enhanced production of IL-6 and MCP-1 but did not effect CRP production. LPS had no effect on collagen and DNA synthesis and alkaline phosphatase activity, however, which suggests that LPS does not affect the physiological properties of PDL cells. Estrogen did not reverse LPS-induced IL-6 and MCP-1 production. The present study suggests that PDL cells in response to LPS via enhanced MCP-1 production contribute to the recruitment of leucocytes to the area of inflammation in periodontitis.

  • 22.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    LPS specifically enhances production of MCP-1 and IL-6 in human periodontal ligament cells2007Conference paper (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to investigate the effects of LPS on the production of chemokines and cytokines in periodontal ligament cells (PDL cells) and if LPS affects functional characteristics of the cells, such as alkaline phosphatase (ALP) activity, collagen and DNA-synthesis. We also assessed if estrogen modulated the LPS-induced responses. Material and Methods: Explants were obtained from the middle third of root surface from teeth extracted for orthodontic reasons. Cells were allowed to migrate from explants and were used in passages 3-4. Aortic tissue was obtained from NMRI mice. Production of monocyte chemoattractant protein-1 (MCP-1), IL-6 and C-reactive protein (CRP) were assessed using ELISA. Transcriptional activity of macrophage inflammatory protein-2 (MIP-2) gene was examined using real-time RT-PCR. ALP activity was measured using a substrate solution and read colormetrically. Collagen and DNA-synthesis were measured using the radiolabeled isotopes proline and thymidine, respectively. The measurements were corrected to the total amount of protein according to the Lowry method. Results: LPS enhanced the production of MCP-1 and IL-6 in PDL cells in a time and dose dependent manner, but had no effect on CRP production. The effects of LPS in PDL cells were not reversed by estrogen. LPS did not affect ALP activity, collagen and DNA-synthesis in PDL cells. LPS enhanced the transcriptional activity of MIP-2 in smooth muscle cells (SMCs). LPS induced MIP-2 was attenuated by a physiological concentration of estrogen (100nM). Conclusion: LPS enhances the production of MCP-1 and IL-6 in PDL cells in a specific manner. LPS induced MCP-1 production in PDL-cells suggests an important role of PDL cells in recruiting leucocytes to the periodontal ligament. Down-regulation of MIP-2 gene by estrogen suggests that estrogen exerts an anti-inflammatory effect via this mechanism.

  • 23.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Nebel, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    LPS-induced MCP-1 and IL-6 production is not reversed by oestrogen in human periodontal ligament cells2008In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 58, no 9, p. 896-902Article in journal (Refereed)
    Abstract [en]

    Department of Periodontology, Faculty of Odontology, Malmö University, SE-205 06 Malmö, Sweden. daniel.jonsson@od.mah.se OBJECTIVE: Periodontal ligament (PDL) cells express oestrogen receptors but the functional importance of oestrogen in PDL cells exposed to bacterial endotoxins is not known. Here we investigate if the inflammation promoter lipopolysaccharide (LPS) affects PDL cell production of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and/or normal functional PDL cell characteristics such as collagen synthesis and cell proliferation and if oestrogen modulates the effects of LPS. METHODS: PDL cells were obtained from periodontal ligament of premolars. PDL cells were treated with Escherichia coli LPS in the absence or presence of oestrogen (17beta-oestradiol, E2). Cellular concentration of IL-6, MCP-1 and CRP was determined by enzyme-linked immunosorbent assay (ELISA). Collagen synthesis was determined by l-[3H]proline incorporation. Cell proliferation was assessed by DNA synthesis measurement using [3H]thymidine incorporation. RESULTS: Stimulation with LPS (500 ng/ml to 10 microg/ml) increased IL-6 production in a concentration-dependent manner. Lower concentration (100 ng/ml) of LPS had no effect. LPS-induced stimulation of IL-6 was not reversed by a physiologically high concentration (100 nM) of E2. LPS increased also MCP-1 production which was unaffected by E2. Treatment with E2 alone had no effect on either IL-6 or MCP-1. Stimulation with LPS had no effect on CRP. LPS did not affect collagen synthesis and cell proliferation, reflecting normal physiological properties of PDL cells. CONCLUSIONS: LPS stimulates PDL cell IL-6 and MCP-1 production but has no effect on the normal physiological properties of PDL cells. LPS-induced IL-6 and MCP-1 is not reversed by oestrogen suggesting that oestrogen exerts no anti-inflammatory effect via this mechanism.

  • 24.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Nebel, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    The human periodontal ligament cell: a fibroblast-like cell acting as an immune cell2011In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 46, no 2, p. 153-157Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Periodontal ligament cells are fibroblast-like cells characterized by collagen production but also possessing some osteoblastic features. In the light of numerous studies presented during recent times, which show that human periodontal ligament cells also produce cytokines and chemokines in response to inflammation promoters, it is reasonable to suggest that periodontal ligament cells play a role as promoters of periodontal inflammation through these mechanisms. MATERIAL AND METHODS: The periodontal ligament, which harbours the periodontal ligament cells, is a part of the attachment apparatus comprised of periodontal ligament cells, extracellular matrix and fibres, attaching the root cement to the alveolar bone. Periodontal ligament cells are in close proximity to bacteria within the plaque and the pocket, and thus these cells are readily accessible to bacterial endotoxins and other promoters of inflammation. RESULTS: Cytokines and chemokines, released by periodontal ligament cells upon stimulation with inflammation promoters, reach the blood vessels easily thanks to rich vascularization of the periodontium stimulating recruitment of white blood cells to the site of inflammation. In addition to classical inflammatory cells, such as leucocytes, macrophages and mast cells, the periodontal ligament cells also contribute to periodontal inflammation via their production and release of cytokines and chemokines. CONCLUSION: Therefore, pharmacological treatment of periodontitis should aim to reduce the release of proinflammatory agents not only from classical inflammatory cells but also from periodontal ligament cells.

  • 25.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Nilsson, Bengt-Olof
    The antimicrobial peptide LL-37 is anti-inflammatory and pro-apoptotic in human periodontal ligament cells2012In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 3, no 47, p. 330-335Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: The antimicrobial peptide LL-37 is expressed in periodontal tissue, and variations in LL-37 levels have been associated with periodontal disease. The effects of LL-37 on periodontal ligament cell function have not been described before. Here, we assess anti-inflammatory properties of LL-37 and investigate the effects of LL-37 on cell differentiation, cell proliferation and apoptosis in human periodontal ligament cells. MATERIAL AND METHODS: Periodontal ligament cells were obtained from teeth extracted for orthodontic reasons. Cytokine (interleukin-6) and chemokine (monocyte chemoattractant protein-1) expression was determined by quantitative PCR, cell differentiation by alkaline phosphatase activity, cell proliferation by counting cells in a Bürker chamber, DNA synthesis by incorporation of radiolabeled thymidine and apoptosis by cell morphology and activated caspase 3 quantities. RESULTS: Treatment with 0.1 and 1 μm of LL-37 totally reversed lipopolysaccharide-induced monocyte chemoattractant protein-1 expression and suppressed lipopolysaccharide-induced interleukin-6 expression by 50-70%. LL-37 had no effect on alkaline phosphatase activity. Incubation with 8 μm LL-37 strongly reduced cell number. DNA synthesis was attenuated by about 90% in response to 8 μm LL-37, confirming its antiproliferative effect. Cell morphology was altered in an apoptosis-like fashion in cells treated with 8 μm LL-37. Furthermore, the quantity of activated caspase 3 was increased in cells treated with 1 and 8 μm of LL-37, suggesting apoptosis. CONCLUSION: LL-37 strongly attenuates lipopolysaccharide-induced cytokine and chemokine expression and, in high concentrations, reduces cell proliferation through inhibition of DNA synthesis and by promoting apoptosis in human periodontal ligament cells.

  • 26.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Nilsson, Jenny
    Odenlund, Malin
    Bratthall, Gunilla
    Broman, Jonas
    Ekblad, Eva
    Lydrup, Marie-Louise
    Nilsson, Bengt-Olof
    Demonstration of mitochondrial oestrogen receptor beta and oestrogen-induced attenuation of cytochrome c oxidase subunit I expression in human periodontal ligament cells2007In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 52, no 7, p. 669-676Article in journal (Refereed)
    Abstract [en]

    Objective: Periodontal ligament (PDL) cells express oestrogen receptor b (ERb) protein, but cellular functions regulated by ERb in these cells have not been identified. In this study we determine if ERb is localised to mitochondria and if oestrogen regulates mitochondrial function in human PDL cells obtained from teeth extracted for orthodontic reasons. Design: Subcellular distribution of ERb was determined by confocal microscopy of cells costained with ERb antibody and the mitochondrion-selective probe MitoTracker and by immunogold electron microscopy. Expression of the mitochondrial enzyme cytochrome c oxidase subunit I, involved in oxidative phosphorylation, was determined by Western blotting in cells treated with or without physiological concentrations of the endogenous oestrogen 17b-oestradiol. Results: ERb immunoreactivity was observed both in the nuclei and the cytoplasm. Mito- Tracker-labelling was observed in the cytoplasm, especially in the perinuclear region, but not in the nuclei. Co-localisation of ERb and MitoTracker was observed in cells derived from both male and female subjects. Mitochondrial localisation of ERb was confirmed by immunogold electron microscopy. Cells treated with or without 17b-oestradiol (100 nM) displayed an identical pattern of staining for mitochondria. Treatment with 100 nM 17b-oestradiol attenuated cytochrome c oxidase subunit I expression by about 30%, while combined treatment with 17b-oestradiol and the ER blocker ICI 182780 (10 mM) had no effect. Conclusion: This study demonstrates mitochondrial localisation of ERb and oestrogeninduced decrease in the expression of cytochrome c oxidase subunit I in human PDL cells, suggesting that oestrogen probably via ERb influences mitochondrial function and PDL cell energy metabolism.

  • 27.
    Jönsson, Daniel
    et al.
    Malmö University, Faculty of Odontology (OD).
    Orho-Melander, M
    Demmer, R T
    Engström, G
    Melander, O
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD).
    Nilsson, P M
    Periodontal disease is associated with carotid plaque area: the Malmö Offspring Dental Study (MODS)2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 287, no 3, p. 301-309Article in journal (Refereed)
    Abstract [en]

    Background: Periodontal disease is associated with cardiovascular disease (CVD) but it is unknown if periodontal disease severity is associated with asymptomatic carotid plaque. The aim of the current population‐based, observational study was to investigate if signs of periodontal disease are associated with the occurrence of carotid plaque and total plaque area (TPA). Methods: The Malmö Offspring Study (MOS) is a population‐based study. MOS participants underwent a thorough cardiovascular phenotyping, including carotid ultrasonography. The Malmö Offspring Dental Study (MODS) invited participants of MOS for dental examination, including periodontal charting. Multivariable regression models were used to analyse the presence of carotid plaque and TPA in relation to periodontal parameters. Results: In all, 831 MODS participants were recruited, out of which 495 belonged to the children generation with mean age of 53 years, 63% had carotid plaque and 38% had moderate or severe periodontal disease. In models adjusted for CVD risk factors, the OR for having carotid plaque in subjects with vs without periodontal disease was 1.75 (95% CI: 1.11–2.78). In a linear model with TPA as dependent and number of periodontal pockets ≥ 4 mm as independent variable, the adjusted beta‐coefficient was 0.34 mm2 (95% CI 0.16–0.52). Conclusion: Individuals within the highest quartile of periodontal pockets are expected to have 9 mm2 larger TPA compared to those without pockets. Our results suggest that intervention studies addressing periodontal disease could be useful for prevention of CVD.

  • 28.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Ramberg, Per
    Demmer, Ryan T
    Kebschull, Moritz
    Dahlén, Gunnar
    Papapanou, Panos N.
    Gingival tissue transcriptomes in experimental gingivitis.2011In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 7, no 38, p. 599-611Article in journal (Refereed)
    Abstract [en]

    AIMS: We investigated the sequential gene expression in the gingiva during the induction and resolution of experimental gingivitis. MATERIAL AND METHODS: Twenty periodontally and systemically healthy non-smoking volunteers participated in a 3-week experimental gingivitis protocol, followed by debridement and 2-week regular plaque control. We recorded clinical indices and harvested gingival tissue samples from four interproximal palatal sites in half of the participants at baseline, Day 7, Day 14 and Day 21 (the "induction phase"), and at Day 21, Day 25, Day 30 and Day 35 in the other half (the "resolution phase"). RNA was extracted, amplified, reversed transcribed, amplified, labelled and hybridized using Affymetrix Human Genome U133Plus2.0 microarrays. Paired t-tests compared gene expression changes between consecutive time points. Gene ontology analyses summarized the expression patterns into biologically relevant categories. RESULTS: The median gingival index was 0 at baseline, 2 at Day 21 and 1 at Day 35. Differential gene regulation peaked during the third week of induction and the first 4 days of resolution. Leucocyte transmigration, cell adhesion and antigen processing/presentation were the top differentially regulated pathways. CONCLUSIONS: Transcriptomic studies enhance our understanding of the pathobiology of the reversible inflammatory gingival lesion and provide a detailed account of the dynamic tissue responses during the induction and resolution of experimental gingivitis.

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  • 29.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Spinell, Thomas
    Vrettos, Anastasios
    Stoecklin-Wasmer, Christin
    Celenti, Romanita
    Demmer, Ryan T.
    Kebschull, Moritz
    Papapanou, Panos N.
    Circulating Endothelial Progenitor Cells in Periodontitis2014In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 85, no 12, p. 1739-1747Article in journal (Refereed)
    Abstract [en]

    Background: Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross-sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis. Methods: A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full-mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle. Results: Levels of hemangioblastic cEPCs were approximately 2.3-fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non-significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P = 0.77), suggesting that they represent independent populations of progenitor cells. Conclusion: These findings further support the notion that oral infections have extraoral effects and document that periodontitis is associated with a mobilization of EPCs from the bone marrow, apparently in response to systemic inflammation and endothelial injury.

  • 30.
    Jönsson, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Wahlin, Åsa
    Malmö högskola, Faculty of Odontology (OD).
    Idvall, I
    Johnsson, I
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Differential Effects of Estrogen on DNA Synthesis in Human Periodontal Ligament and Breast Cancer Cells2005In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 40, no 5, p. 401-406Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is important to clarify the biological function of the female sex hormones estrogen and progesterone in periodontal ligament cells, as these hormones may affect periodontal health. We have previously shown that human periodontal ligament cells express estrogen receptor beta (ERbeta) but not ERalpha, whereas human breast cancer cells (MCF7) express both ERalpha and ERbeta. Data on progesterone receptor (PgR) expression in human periodontal ligament cells have not been reported. OBJECTIVES: Determine PgR expression in human periodontal ligament and MCF7 cells and to investigate how estrogen affects DNA and collagen synthesis in these two cell types showing different pattern of expression for ERalpha and beta. METHODS: Periodontal ligament cells were obtained from the periodontal ligament of premolars extracted for orthodontic reasons and MCF7 cells from the American Type Culture Collection (ATCC). PgR expression was determined by immunocytochemistry. DNA and collagen synthesis was determined by [(3)H]thymidine and L-[(3)H]proline incorporation, respectively. RESULTS: PgR immunoreactivity was observed in nuclei of MCF7 but not periodontal ligament cells. Treatment with estrogen (17beta-estradiol, E(2)) at physiological concentrations for 24 h stimulated DNA synthesis by more than two times in MCF7 cells, whereas there was no effect on periodontal ligament cell DNA synthesis. The ER blocker ICI 182780 fully reversed the stimulatory effect of E(2). Not only short-term (24 h) but also long-term (5 days) treatment with E(2) lacked effect on DNA synthesis in periodontal ligament cells. Neither periodontal ligament cell viability nor collagen synthesis was affected by E(2) treatment. Identical results were observed in periodontal ligament cells from male and female subjects. CONCLUSIONS: Human MCF7 but not periodontal ligament cells express PgR, suggesting that progesterone via PgR affects MCF7 but not periodontal ligament cells. Further, estrogen stimulates breast cancer MCF7 cell proliferation, whereas it has no effect on proliferation of periodontal ligament cells, probably reflecting cell type specific ER expression pattern in these two cell types.

  • 31.
    Nebel, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Genes regulated by estrogen in human PDL cells by whole genome arrays2009Conference paper (Other academic)
    Abstract [en]

    Background: The periodontal ligament cells (PDL cells) play a key role in the formation of the periodontal ligament but these cells have other functions as well. The PDL cells express estrogen receptors but the functional importance is not known. Estrogen modulates inflammation and our hypothesis is that estrogen protects the periodontium via an anti-inflammatory effect on PDL cells. Aim: To identify genes regulated by estrogen in LPS-treated human PDL cells by whole genome arrays. Materials and methods: PDL cells were obtained from human premolars extracted for orthodontic reasons. The cells were divided into two groups. One group was pre-treated with 17ÿ-estradiol (E2, 100 nM) for 2 h and then with Escherichia coli LPS (500ng/ml) for 24 h. The other group was treated with LPS only. Total RNA was extracted and purified by RNeasy Mini Kit (Qiagen®, USA). A whole genome microarray was performed (Affymetrix®, USA) comparing gene expression in the two groups. The cut-off limit was set to a twofold change. Results and Conclusion: Estrogen caused an up-regulation of 38 genes, while 28 genes were down-regulated. Estrogen regulated genes associated with cell-metabolism and cell-signalling but also genes associated with early the inflammatory response. The functional significance of these findings is now determined by e.g. measuring protein levels with ELISA. We conclude that estrogen regulates gene expression in human PDL cells exposed to LPS.

  • 32.
    Nebel, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Norderyd, Ola
    Malmö högskola, Faculty of Odontology (OD).
    Bratthall, Gunilla
    Nilsson, Bengt-Olof
    Differential regulation of chemokine expression by estrogen in human periodontal ligament cells2010In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 45, no 6, p. 796-802Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Estrogen modulates inflammatory responses, but the mechanisms involved have not yet been identified. Periodontal ligament (PDL) cells produce chemokines (a group of chemoattractant molecules that recruit leukocytes) and it has been suggested that estrogen modulates periodontal inflammation by regulating the expression of chemokines by PDL cells. Therefore, the objectives of this study were to investigate the regulation of chemokine ligand 2 [CCL2/monocyte chemoattractant protein 1 (MCP-1)], chemokine ligand 3 [CCL3/macrophage inflammatory protein-1α (MIP-1α)] and chemokine ligand 5 (CCL5/RANTES) by estrogen in human PDL cells. MATERIAL AND METHODS: PDL cells were obtained from the PDL of premolars, extracted for orthodontic reasons, from two boys and two girls (16 and 17 years of age). PDL cell CCL2, CCL3 and CCL5 mRNA transcripts were determined by quantitative real-time PCR. The concentrations of CCL2, CCL3 and CCL5 proteins were determined by ELISAs. RESULTS: Treatment with 0.5 μg/mL of lipopolysaccharide (LPS, from Escherichia coli) + 100 nm 17β-estradiol (E(2) ) for 24 h reduced the expression of CCL3 mRNA by about 40% compared to PDL cells treated with LPS alone. Attenuation of CCL3 mRNA was not associated with a decrease in CCL3 protein within 48 h, suggesting a slow turnover of the CCL3 protein. Interindividual differences in the effects of E(2) on CCL5 mRNA expression were observed. E(2) (100 nm) increased the expression of CCL5 by 40-60% in PDL cells derived from two subjects but reduced the expression of CCL5 by about 30% in cells from another subject. CCL2 mRNA and CCL2 protein were highly expressed, but not regulated by E(2) . Similar data were observed in cells obtained from both boys and girls. CONCLUSION: Regulation, by estrogen, of chemokine expression in PDL cells shows a complex pattern involving the down-regulation as well as the up-regulation of chemokines, suggesting that estrogen exerts both anti-inflammatory and proinflammatory effects through these mechanisms.

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  • 33.
    Nebel, Daniel
    et al.
    Malmö högskola, Faculty of Odontology (OD).
    Svensson, D.
    Arosenius, Karin
    Malmö högskola, Faculty of Odontology (OD).
    Larsson, E.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Nilsson, B. -O.
    1α,25-dihydroxyvitamin D3 promotes osteogenic activity and downregulates proinflammatory cytokine expression in human periodontal ligament cells2015In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 50, no 5, p. 666-673Article in journal (Refereed)
    Abstract [en]

    Background and ObjectiveThe aim of this study was to assess the impact of 1,25-dihydroxyvitamin D3 (vitamin D3) on osteogenic and inflammatory properties of human periodontal ligament (PDL) cells and investigate underlying mechanisms. Material and MethodsHuman PDL cells, obtained from four subjects, were stimulated with vitamin D3 for 4-48h. The bone markers osteopontin and osteocalcin and proinflammatory cytokine/chemokine expression was determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Cytokine and chemokine expression was determined after stimulation with the inflammation promoter lipopolysaccharide (LPS) in the presence or absence of vitamin D3. Alkaline phosphatase activity was assessed using p-nitrophenylphosphate substrate. ResultsTreatment with 30ng/mL of vitamin D3, corresponding to an optimal plasma concentration of vitamin D, for 24h had no effect on PDL cell number and morphology but increased PDL cell osteopontin and osteocalcin mRNA expression by about 70 and 40%, respectively, and, moreover, treatment with vitamin D3 for 48h enhanced PDL cell alkaline phosphatase activity by about two times showing that vitamin D3 exerts pro-osteogenic effects in human PDL cells. Stimulation with LPS (1g/mL) for 4h increased PDL cell interleukin (IL)-6 cytokine and chemokine ligand 1 (CXCL1) chemokine mRNA expression several fold. The LPS-induced increase in IL-6 and CXCL1 transcripts was attenuated by vitamin D3 (30ng/mL). Treatment with vitamin D3 (3-300ng/mL) for 24h reduced the LPS-evoked increase in PDL cell IL-6 protein by about 50%. Vitamin D3 (30ng/mL) had no effect on LPS-induced IL-1 and MCP-1 mRNA expression. ConclusionsVitamin D3 promotes osteogenic differentiation but also downregulates inflammation promoter-induced IL-6 cytokine and CXCL1 chemokine expression in human PDL cells, suggesting that vitamin D3 both stimulates bone regeneration and antagonizes inflammation in human periodontal tissue.

  • 34.
    Ottosson, Filip
    et al.
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
    Hultgren, Lina
    Malmö University, Faculty of Odontology (OD). Public Dental Service of Skåne, Lund, Sweden.
    Fernandez, Celine
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Engström, Gunnar
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Orho-Melander, Marju
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Kennbäck, Cecilia
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Persson, Margaretha
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Demmer, Ryan T
    School of Public Health, University of Minnesota, Minneapolis, MN, USA; Mailman School of Public Health, Columbia University, NY, USA.
    Melander, Olle
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD). Department of Dental Medicine, Karolinska Institutet, Solna, Sweden.
    Nilsson, Peter
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Public Dental Service of Skåne, Lund, Sweden.
    The inverse association between a fish consumption biomarker with gingival inflammation and periodontitis: a population-based study2022In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 49, no 4, p. 353-361Article in journal (Refereed)
    Abstract [en]

    AIM: The metabolite 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish-intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as extent and severity variables.

    METHODS: The Malmö Offspring Study (MOS) is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography-mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, BMI, fasting glucose and smoking.

    RESULTS: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (beta -2.12, p=0.002), and lower odds of severe periodontitis (OR 0.74, 95% CI=0.56-0.98). Higher CMPF levels were also associated with more teeth (beta 0.19, p=0.001), lower number of periodontal pockets (>4 mm) (beta -1.07, p=0.007) and lower odds of having two or more >6 mm periodontal pockets (OR 0.80, 95% CI=0.65-0.98) in fully adjusted models.

    CONCLUSION: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out and future studies are warranted. This article is protected by copyright. All rights reserved.

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  • 35. Rafferty, Brian
    et al.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Kalachikov, Sergey
    Demmer, Ryan T.
    Nowygrod, Roman
    Elkind, Mitchell S.V.
    Bush, Harry
    Kozarov, Emil
    Impact of monocytic cells on recovery of uncultivable bacteria from atherosclerotic lesions2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 273-280Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Epidemiological evidence suggests that infections may contribute to atherogenesis. However, with the exception of Chlamydophila pneumoniae, cultivable bacteria have not been recovered from atherosclerotic lesions. Therefore, we aimed at developing an approach to recover uncultivable bacteria from atherectomy tissues. METHODS: We cultured homogenates from atherectomy specimens from seven nonseptic patients undergoing surgery for arterial obstruction either alone or together with THP-1 monocyte-like cells. We performed 16S rDNA analysis, biochemical tests, random amplification of polymorphic DNA PCR analysis, quantitative polymerase chain reaction (qPCR) and immunohistofluorescence to identify the cultivated bacteria. Wilcoxon signed-rank tests were used to determine whether THP-1 treatment yielded a higher number of isolates than did the untreated controls. RESULTS: We recovered more bacteria from cocultures of atherectomy specimens with THP-1 cells than atherectomy specimens cultured alone. On average, tissue homogenates incubated with THP-1 cells versus control yielded 124 vs. 22 colony-forming units, a median of 140 vs. 7, respectively (P = 0.02). We recovered 872 isolates of limited number of species, including Propionibacterium acnes, Staphylococcus epidermidis and Streptococcus infantis and the fastidious anaerobe Porphyromonas gingivalis, and confirmed its presence in tissue using double immunofluorescence imaging. qPCR demonstrated the presence of ≥3.5 × 10(3) P. gingivalis genomes per gram of atheromatous tissue. CONCLUSIONS: These results indicate that viable previously uncultivable bacterial species are present within atheromas. Our results suggest revisiting the hypothesis that infections may have a causative role in atherosclerotic inflammation and have implications for research regarding novel diagnostics and treatments for cardiovascular disease.

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  • 36.
    Rosland, Anders
    et al.
    Univ Bergen, Dept Clin Dent, Sect Prosthodont, N-5009 Bergen, Norway..
    Bertelsen, Randi J.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Oral Hlth Ctr Expertise Western Norway, Bergen, Norway..
    Bunaes, Dagmar F.
    Univ Bergen, Dept Clin Dent, Sect Prosthodont, N-5009 Bergen, Norway..
    Drengenes, Christine
    Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD). Karolinska Inst, Dept Dent Med, Huddinge, Sweden..
    Lie, Stein-Atle
    Univ Bergen, Dept Clin Dent, Sect Prosthodont, N-5009 Bergen, Norway..
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Lund Univ, Dept Clin Sci, Malmö, Sweden.;Publ Dent Serv Skane, Lund, Sweden..
    Malinovschi, Andrei
    Uppsala Univ, Dept Med Sci, Clin Physiol, Uppsala, Sweden..
    Periodontitis is associated with airflow obstruction in the Malmö Offspring Dental Study2024In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 51, no 1, p. 86-96Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the association between periodontitis and lung function in the Malmo Offspring Dental Study.Materials and Methods: In all 1001 individuals (49.9% female, mean age: 44.6) from Malmo Offspring Dental Study were included. Periodontitis was assessed by a full-mouth examination protocol including bleeding on probing and classified according to the American Academy of Periodontology/Center for Disease Control definitions. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were expressed as absolute values and %predicted according to Global Lung Function Initiative reference values. FEV1, FVC and FEV1/FVC were analysed in relation to periodontal status using linear regression.Results:Severe periodontitis was found in 7% of the population. Adjusted regression models showed significant associations between lung function and severe periodontitis with 2.1 unit lower FEV1/FVC ratio (95% CI: -3.91, -0.23) and odds ratio (adjusted) of 2.56 (95% CI: 1.40, 4.75, p = .003) for airflow obstruction (FEV1/FVC less than the lower limit of normal) if having severe periodontitis. Lower values of %predicted FEV1 and %predicted FVC, but not FEV1/FVC, were found in individuals with >25% bleeding on probing.Conclusions: Severe periodontitis was associated with lower FEV1/FVC ratio and airflow obstruction in the present cohort. More large-scale prospective studies and intervention studies are required for a comprehensive evaluation.

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  • 37.
    Sayardoust, Shariel
    et al.
    School of Health and Welfare, Jönköping University, Jönköping, Sweden; Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Anders
    Division of Molecular Periodontology, Department of Odontology, Umeå University, Umeå, Sweden.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Odontology and Oral Health, Public Dental Care of Skåne, Lund, Sweden.
    Do Probiotics Cause a Shift in the Microbiota of Dental Implants-A Systematic Review and Meta-Analysis.2022In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 12, article id 823985Article in journal (Refereed)
    Abstract [en]

    Objective: The primary aim of this current systematic review and meta-analysis was to evaluate the potential microbiological effect of probiotics on the implant microbiota. The secondary aim was to evaluate if probiotics have any effect as an adjunct to non-surgical peri-implant treatment in reducing peri-implant mucositis and peri-implantitis clinical parameters-bleeding on probing, modified Gingival Index, and pocket depth.

    Methods: the PubMed, Scopus, and Web of Science Core Collection databases was conducted. Two independent reviewers screened the reports based on the PICO criteria-inclusion and exclusion criteria.

    Results: In total, 467 records were identified, and ultimately, 7 papers were included: 3 papers in the qualitative synthesis of microbiological effect and 4 in the meta-analysis synthesis on pocket depth. The data synthesis showed that probiotics had no detectable effect on the implant microflora, and in the following data synthesis, no clinical peri-implantitis variable showed a significantly beneficial effect from probiotics in the test group compared to the control group.

    Conclusion: Within the limitations of this review, the oral implant microflora is not affected by probiotics nor do probiotics add any effect to the conventional non-surgical treatment of peri-implant mucositis and peri-implantitis.

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  • 38.
    Sayols-Baixeras, Sergi
    et al.
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden.;CIBER Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain (S.S.-B.)..
    Dekkers, Koen F.
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden..
    Baldanzi, Gabriel
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden..
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.).;Public Dental Service of Skåne, Lund, Sweden (D.J.)..
    Hammar, Ulf
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden.;Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.)..
    Lin, Yi-Ting
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden.;Division of Family Medicine and Primary Care, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Huddinge, Sweden (Y.-T.L., J.Ä.)..
    Ahmad, Shafqat
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden.;Preventive Medicine Division, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA (S.A.)..
    Nguyen, Diem
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden..
    Varotsis, Georgios
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden..
    Pita, Sara
    Clinical Microbiomics A/S, Copenhagen, Denmark (S.P., N.N., A.C.E., J.B.H., H.B.N.).;The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark (S.P.)..
    Nielsen, Nynne
    Clinical Microbiomics A/S, Copenhagen, Denmark (S.P., N.N., A.C.E., J.B.H., H.B.N.)..
    Eklund, Aron C.
    Clinical Microbiomics A/S, Copenhagen, Denmark (S.P., N.N., A.C.E., J.B.H., H.B.N.)..
    Holm, Jacob B.
    Clinical Microbiomics A/S, Copenhagen, Denmark (S.P., N.N., A.C.E., J.B.H., H.B.N.)..
    Nielsen, H. Bjørn
    Clinical Microbiomics A/S, Copenhagen, Denmark (S.P., N.N., A.C.E., J.B.H., H.B.N.)..
    Ericson, Ulrika
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.)..
    Brunkwall, Louise
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.).;Clinical Studies Sweden, Forum Söder, Region Skåne, Lund, Sweden (L.B.)..
    Ottosson, Filip
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.).;Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark (F.O.)..
    Larsson, Anna
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.)..
    Ericson, Dan
    Malmö University, Faculty of Odontology (OD).
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD). DDepartment of Dental Medicine, Karolinska Institutet, Solna, Sweden (B.K.)..
    Nilsson, Peter M.
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.).;Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden (P.M.N.)..
    Malinovschi, Andrei
    Clinical Physiology (A.M.), Department of Medical Sciences, Uppsala University, Sweden..
    Lind, Lars
    Clinical Epidemiology (L.L., J.S.), Department of Medical Sciences, Uppsala University, Sweden..
    Bergström, Göran
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (G. Bergström).;Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden (G. Bergström)..
    Sundström, Johan
    Clinical Epidemiology (L.L., J.S.), Department of Medical Sciences, Uppsala University, Sweden.;The George Institute for Global Health, University of New South Wales, Sydney, Australia (J.S.)..
    Ärnlöv, Johan
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Huddinge, Sweden (Y.-T.L., J.Ä.).;School of Health and Social Studies, Dalarna University, Falun, Sweden (J.Ä.)..
    Engström, Gunnar
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.)..
    Smith, J. Gustav
    The Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Sweden (J.G.S.)..
    Orho-Melander, Marju
    Department of Clinical Sciences in Malmö, Lund University, Sweden (D.J., U.E., L.B., F.O., A.L., P.M.N., G.E., M.O.-M.)..
    Fall, Tove
    Molecular Epidemiology and Science for Life Laboratory (S.S.-B., K.F.D., G. Baldanzi, U.H., Y.-T.L., S.A., D.N., G.V., T.F.), Department of Medical Sciences, Uppsala University, Sweden..
    Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort2023In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 148, no 6, p. 459-472Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.

    METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.

    RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.

    CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

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  • 39.
    Schwarz, Frank
    et al.
    Department of Oral Surgery and Implantology Goethe University Frankfurt Germany.
    Alcoforado, Gil
    Clinical Research Unit Egas Moniz University Almada Portugal.
    Guerrero, Adrian
    Private Periodontal Practice Marbella Spain.
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Department of Clinical Sciences Medical Faculty Lund University Malmö Sweden;Public Dental Service of Skåne Lund Sweden.
    Klinge, Björn
    Malmö University, Faculty of Odontology (OD). Department of Dental Medicine Division of Oral Diseases Karolinska Institute Stockholm Sweden.
    Lang, Niklaus
    Department of Periodontology School of Dental Medicine University of Bern Bern Switzerland.
    Mattheos, Nikos
    Department of Oral and Maxillofacial Surgery Faculty of Dentistry Chulalongkorn University Bangkok Thailand;Department of Dental Medicine Karolinska Institute Stockholm Sweden.
    Mertens, Brenda
    Department of Periodontology, Oral and Implant Surgery University of Liege Liège Belgium;Private practice Montpellier France.
    Pitta, João
    Division of Fixed Prosthodontics and Biomaterials University Clinics of Dental Medicine University of Geneva Geneva Switzerland.
    Ramanauskaite, Ausra
    Department of Oral Surgery and Implantology Goethe University Frankfurt Germany.
    Sayardoust, Shariel
    Department of Biomaterials Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Sweden.
    Sanz‐Martin, Ignacio
    Private practice Lausanne Switzerland.
    Stavropoulos, Andreas
    Malmö University, Faculty of Odontology (OD). Division of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna Vienna Austria;Division of Regenerative Dentistry and Periodontology University Clinics of Dental Medicine (CUMD) University of Geneva Geneva Switzerland.
    Heitz‐Mayfield, Lisa
    International Research Collaborative – Oral Health and Equity School of Anatomy, Physiology and Human Biology The University of Western Australia, Crawley Perth WA Australia.
    Peri‐implantitis: Summary and consensus statements of group 3. The 6th EAO Consensus Conference 20212021In: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 32, no S21, p. 245-253Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the influence of implant and prosthetic components on peri-implant tissue health. A further aim was to evaluate peri-implant soft-tissue changes following surgical peri-implantitis treatment.

    MATERIALS AND METHODS: Group discussions based on two systematic reviews (SR) and one critical review (CR) addressed (i) the influence of implant material and surface characteristics on the incidence and progression of peri-implantitis, (ii) implant and restorative design elements and the associated risk for peri-implant diseases, and (iii) peri-implant soft-tissue level changes and patient-reported outcomes following peri-implantitis treatment. Consensus statements, clinical recommendations, and implications for future research were discussed within the group and approved during plenary sessions.

    RESULTS: Data from preclinical in vivo studies demonstrated significantly greater radiographic bone loss and increased area of inflammatory infiltrate at modified compared to non-modified surface implants. Limited clinical data did not show differences between modified and non-modified implant surfaces in incidence or progression of peri-implantitis (SR). There is some evidence that restricted accessibility for oral hygiene and an emergence angle of >30 combined with a convex emergence profile of the abutment/prosthesis are associated with an increased risk for peri-implantitis (CR). Reconstructive therapy for peri-implantitis resulted in significantly less soft-tissue recession, when compared with access flap. Implantoplasty or the adjunctive use of a barrier membrane had no influence on the extent of peri-implant mucosal recession following peri-implantitis treatment (SR).

    CONCLUSIONS: Prosthesis overcontouring and impaired access to oral hygiene procedures increases risk for peri-implantitis. When indicated, reconstructive peri-implantitis treatment may facilitate the maintenance of post-operative peri-implant soft-tissue levels.

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  • 40.
    Sundh, Josefin
    et al.
    Örebro Univ, Fac Med & Hlth, Dept Resp Med, S-70185 Örebro, Sweden..
    Tanash, Hanan
    Lund Univ, Skane Univ Hosp, Dept Resp Med, Malmö, Sweden..
    Arian, Rahi
    Publ Dent Hlth Serv, Dept Periodontol & Implantol, Örebro, Sweden..
    Neves-Guimaraes, Alessandra
    Publ Dent Hlth Serv, Dept Periodontol & Implantol, Örebro, Sweden..
    Broberg, Katrin
    Publ Dent Serv Skane, Lund, Sweden..
    Lindved, Gustav
    Clin Microbi, Copenhagen, Denmark..
    Kern, Timo
    Clin Microbi, Copenhagen, Denmark..
    Zych, Konrad
    Clin Microbi, Copenhagen, Denmark..
    Nielsen, Henrik Bjørn
    Clin Microbi, Copenhagen, Denmark..
    Halling, Anders
    Lund Univ, Ctr Primary Hlth Care Res, Dept Clin Sci Malmö, Malmö, Sweden..
    Ohlsson, Bodil
    Lund Univ, Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Jönsson, Daniel
    Malmö University, Faculty of Odontology (OD). Publ Dent Serv Skane, Lund, Sweden.;Lund Univ, Dept Clin Sci Malmö, Hypertens & Cardiovasc Dis, Malmö, Sweden..
    Advanced Dental Cleaning is Associated with Reduced Risk of COPD Exacerbations-A Randomized Controlled Trial2021In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 16, p. 3203-3215Article in journal (Refereed)
    Abstract [en]

    Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes. Patients and Methods: One-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student's t-test and Mann- Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models. Results: In the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25-0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10-0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723). Conclusion: Advanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

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  • 41. Svensson, Daniel
    et al.
    Westman, Johannes
    Wickström, Claes
    Malmö högskola, Faculty of Odontology (OD).
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Herwald, Heiko
    Nilsson, Bengt-Olof
    Human endogenous peptide p33 inhibits detrimental effects of LL-37 on osteoblast viability2015In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 50, no 1, p. 80-88Article in journal (Refereed)
    Abstract [en]

    Background and Objective: High levels of the antimicrobial peptide, LL-37, are detected in gingival crevicular fluid from patients with chronic periodontitis. LL-37 not only shows antimicrobial activity but also affects host-cell viability. The objective of the present study was to identify endogenous mechanisms that antagonize the detrimental effects of LL-37 on osteoblast viability, focusing on the human peptide p33 expressed on the surface of various cell types. Material and Methods: Human osteoblast-like MG63 cells and human hFOB1.19 osteoblasts were treated with or without LL-37 in the presence or absence of p33. Recombinant human p33 was expressed in an Escherichia coli expression system. Lactate dehydrogenase (LDH) was assessed using an enzymatic spectrophotometric assay. DNA synthesis was determined by measuring [3H]-thymidine incorporation. Cell number was assessed by counting cells in a Bu€rker chamber. Intracellular Ca2+ was monitored by recording Fluo 4-AM fluorescence using a laser scanning confo- cal microscope. Cellular expression of p33 was determined by western blotting. Results: LL-37 caused a concentration-dependent release of LDH from human osteoblasts, showing a half-maximal response value (EC50) of 4 lM and a rapid and sustained rise in the intracellular Ca2+ concentration of osteoblasts, sug- gesting that LL-37 forms pores in the cell membrane. p33 (10 lM) inhibited the LL-37-induced LDH release and LL-37-evoked rise in intracellular Ca2+ con- centration, suggesting that p33 prevents LL-37-induced permeabilization of the cell membrane. Moreover, p33 blocked LL-37-induced attenuation of osteoblast numbers. Also, mucin antagonized, at concentrations representative for nonsti- mulated whole saliva, LL-37-evoked LDH release, whilst cationic endogenous polyamines had no impact on LL-37-induced LDH release from osteoblasts. Conclusions: The endogenous peptide p33 prevents LL-37-induced reduction of human osteoblast viability. Importantly, this mechanism may protect the osteo- blasts from LL-37-induced cell damage in patients suffering from chronic peri- odontitis associated with high levels of LL-37 locally.

  • 42. Säll, Johanna
    et al.
    Carlsson, Martin
    Gidlöf, Olof
    Holm, Anders
    Humlén, Johan
    Öhman, Jenny
    Svensson, Daniel
    Nilsson, Bengt-Olof
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    The antimicrobial peptide LL-37 alters human osteoblast Ca2+ handling and induces Ca2+-independent apoptosis2013In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 3, no 5, p. 290-300Article in journal (Refereed)
    Abstract [en]

    The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC50 value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca(2+) concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca(2+) also in the presence of the respective L- and T-type voltage-sensitive Ca(2+) channel blockers nifedipine and NiCl2. LL-37 had no effect on Ca(2+) in cells incubated with Ca(2+)-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca(2+) in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca(2+) inflow via a mechanism independent of voltage-sensitive Ca(2+) channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca(2+).

  • 43. Örtorp, Anders
    et al.
    Jönsson, Daniel
    Malmö högskola, Faculty of Odontology (OD).
    Mouhsen, Alaa
    Vult von Steyern, Per
    Malmö högskola, Faculty of Odontology (OD).
    The fit of cobalt-chromium three-unit fixed dental prostheses fabricated with four different techniques: A comparative in vitro study2011In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 27, no 4, p. 356-363Article in journal (Refereed)
    Abstract [en]

    This study sought to evaluate and compare the marginal and internal fit in vitro of three-unit FDPs in Co-Cr made using four fabrication techniques, and to conclude in which area the largest misfit is present. METHODS: An epoxy resin master model was produced. The impression was first made with silicone, and master and working models were then produced. A total of 32 three-unit Co-Cr FDPs were fabricated with four different production techniques: conventional lost-wax method (LW), milled wax with lost-wax method (MW), milled Co-Cr (MC), and direct laser metal sintering (DLMS). Each of the four groups consisted of eight FDPs (test groups). The FDPs were cemented on their cast and standardised-sectioned. The cement film thickness of the marginal and internal gaps was measured in a stereomicroscope, digital photos were taken at 12× magnification and then analyzed using measurement software. Statistical analyses were performed with one-way ANOVA and Tukey’s test. RESULTS: Best fit based on the means (SDs) in μm for all measurement points was in the DLMS group 84 (60) followed by MW 117 (89), LW 133 (89) and MC 166 (135). Significant differences were present between MC and DLMS (p<0.05). The regression analyses presented differences within the parameters: production technique, tooth size, position and measurement point (p<0.05). SIGNIFICANCE: Best fit was found in the DLMS group followed by MW, LW and MC. In all four groups, best fit in both abutments was along the axial walls and in the deepest part of the chamfer preparation. The greatest misfit was present occlusally in all specimens.

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