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Caries correlates strongly with salivary levels of Matrix Metalloproteinase-8
Malmö högskola, Faculty of Odontology (OD).ORCID iD: 0000-0001-6720-3900
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2015 (English)In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 49, no 1, p. 1-8, article id 49Article in journal (Refereed)
Abstract [en]

The caries process in dentin involves the degradation of both mineral and organic matrix. The demineralization has been demonstrated to be caused by bacterial acids. How-ever, the collagen degradation is considered to be initiated by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). This paper aims to relate salivary MMP-8 (or salivary collagenase-2) and tissue inhibi-tor of MMP (TIMP-1) levels to manifest caries in a large num-ber of subjects. A random sample of 451 adults (aged 18-87 years) living in the south of Sweden was included in this study. Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentra-tions of MMP-8, TIMP-1 and total protein, using an immuno-fluorometric assay, an enzyme-linked immunosorbent assay and the Bradford assay, respectively. Salivary numbers of mutans streptococci and lactobacilli were determined using a chair-side kit. Subjects with manifest caries lesions present-ed with elevated levels of MMP-8 (p < 0.001) as well as total protein, MMP-8/TIMP-1 ratio, bleeding on probing and plaque index (p = 0.05) compared with subjects without manifest caries. Multiple linear regression analysis with car-ies as the dependent variable revealed MMP-8 as the only significant explanatory variable (p < 0.001). TIMP-1 was not significant in any case. Using MMP-8 as the dependent vari-able revealed total protein concentration, caries lesions (p ≤ 0.001) and salivary secretion rate (p = 0.05) as explanatory variables. In conclusion, our data reveal that subjects with manifest caries lesions have elevated levels of salivary MMP-8 relative to subjects with no caries lesions.

Place, publisher, year, edition, pages
S. Karger, 2015. Vol. 49, no 1, p. 1-8, article id 49
Keywords [en]
Dental caries, Dentin, Matrix metalloproteinase-8, Saliva, Tissue inhibitor of metalloproteinase-1
National Category
Dentistry
Identifiers
URN: urn:nbn:se:mau:diva-6021DOI: 10.1159/000360625ISI: 000346584800001PubMedID: 25096527Scopus ID: 2-s2.0-84923617486Local ID: 18618OAI: oai:DiVA.org:mau-6021DiVA, id: diva2:1402909
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2024-02-05Bibliographically approved
In thesis
1. Dentine caries: acid tolerant microorganisms and aspects on collagen degradation
Open this publication in new window or tab >>Dentine caries: acid tolerant microorganisms and aspects on collagen degradation
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Karies är en stor folksjukdom, trots att den både kan förebyggas och behandlas effektivt. Om man inte ingriper preventivt och låter det naturliga förloppet råda, kommer kariesangreppet till slut att bryta igenom emaljen och involvera även den underliggande dentinvävnaden. Kariessjukdomen orsakas av orala mikroorganismer, som en konsekvens av dessas nedbrytning av kostrelaterade kolhydrater. Som en biprodukt bildas då syror som löser upp (demineraliserar tandvävnaden), så att synliga hål till slut bildas. Syran kan lösa upp mineralfasen i tanden, men dentin består även till stor del av kollagen, vilket inte kan lösas upp av enbart syror. Man hänförde länge detta till proteinnedbrytande bakterier, men det har visat sig att munhålebakterierna inte har förmågan att lösa upp kollagen, och man tror nu att denna nedbrytning sker med hjälp av kroppsegna enzymer, bland annat matrix metalloproteinaser (MMP). De biologiska mekanismerna bakom kollagennedbrytning vid dentinkaries är emellertid dåligt undersökta, och delar av denna rapport (Studie III och IV) inriktar sig därför på detta område. Syran som bakterierna bildar skapar också en sur närmiljö för dem själva, vilket gör det svårt för dem att överleva, särskilt i ett begränsat utrymme som ett kariesangrepp. Man har länge ansett att endast vissa specifika bakterier har förmågan att leva och trivas i sura miljöer, men nya studier har ifrågasatt detta. I denna rapport (Studie II) undersöks även förekomsten av syratåliga bakterier på olika nivåer i dentinkariesangrepp med hjälp av en ny metod. Målet vid avlägsnande av karies är att ta bort fullständigt förstörd tandvävnad, men att försöka spara så mycket som möjligt av den delvis skadade vävnaden, vilken kan återställas. Detta har också aktualiserats då nya operativa principer och material lanserats under den senaste tioårsperioden. Det är emellertid svårt att avgöra var gränsen går kliniskt, och ett sätt att mäta dentinets ”friskhet” kan vara att mäta antalet bakterier i vävnaden. I den första rapporten (Studie I) undersöks den kvarvarande bakterieförekomsten efter kariesborttagning med två olika operativa metoder. Avhandlingen söker svar på följande frågeställningar: Studie I. Finns det några skillnader vad gäller antal kvarvarande bakterier efter dentinkariesavlägsnande med mekanisk (vanligt borr) eller kemo-mekanisk (Carisolv) metod? Studie II. Hur ser sammansättningen av den syratåliga bakteriefloran ut på tre olika nivåer i olika dentinkariesangrepp? Studie III. Finns det något samband mellan förekomsten av etablerade kariesangrepp och nivåerna av enzymet MMP-8 och dess nedreglerande protein TIMP-1 i saliv? Studie IV. Kan man framställa demineraliserat dentinmatrix med bibehållen biologisk aktivitet inför framtida studier av mekanismerna bakom nedbrytning av kollagen vid dentinkaries? Vad händer spontant med detta demineraliserade dentinmatrix över tid? Huvudfynden i studierna är: 1. Båda metoderna för att avlägsna dentinkaries minskade bakterieantalet radikalt. Det finns dock alltid kvar små mängder av bakterier i kaviteten. 2. Alla de undersökta kaviteterna hade en unik sammansättning av syratåliga bakterier, både till typ och antal, vilket indikerar att ett flertal olika bakterier har förmågan att anpassa sig till sura miljöer och potentiellt bidra till kariesutvecklingen. Vidare, fungerade de pH-specifika odlingsmedierna väl för att få fram de syratåliga bakterierna, något som är svårt med konventionella metoder. 3. Försökspersoner med etablerade dentinkariesangrepp uppvisade mycket högre förekomst av MMP-8 i saliven jämfört med kariesfria försökspersoner. Det nedreglerande proteinet TIMP-1 uppvisade inga samband alls. 4. Dentinmatrix framställt med båda testmetoderna uppvisade förekomst av intakt kollagen, samt aktivt MMP-8. Vidare så uppvisades en spontan nedbrytning av kollagen över tid, vilket tolkades som mestadels ett resultat av det aktiva MMP-8 enzymet. De nyvunna grundkunskaperna bildar underlag för nya studier inom forskningsområdet, samt för nya behandlingsmetoder, framför allt sådana som skulle kunna moderera eller förhindra dentinkariesprogression.

Abstract [en]

Dental caries is a common disease all over the world, despite the fact that it can be both effectively prevented as well as treated. It is driven by acids produced by oral microorganisms as a consequence of their metabolism of dietary carbohydrates. Given enough acid challenge, eventually the enamel barrier will be broken down, and the carious lesion will extend into underlying hard tissue, forming a macroscopic cavity in the dentine. In comparison to plaque biofilm on enamel, this dentine carious lesion will form a vastly different environment for the residing microorganisms. The environment will influence the types and numbers of microorganisms that will be able to colonize the dentine caries lesion. The overall aims for this thesis is to enumerate and further study microorganisms found in established dentine caries lesions, and also to illuminate how host-derived proteolytic enzymes might contribute to this degradation, in order to better understand the caries process in dentine, but also to find incitements for new methods to influence the natural progression of caries lesions. In Paper I, the number of remaining viable microorganisms after completed excavation using two different excavation methods were investigated. Samples of carious dentine tissue was collected before and after excavation, and cultivated on different agar media in different atmospheres. Analysis was performed by counting the number of colony forming units (cfu). Key findings: Numbers of remaining microorganisms after excavation was low for both methods, but some microorganisms always remained in the cavity floors even when the cavities were judged as ”caries free” using normal clinical criteria. In Paper II, the acid tolerant microbiota in established dentine caries lesions were investigated. Samples were taken as in Paper I, but on three levels (superficial, center of lesion, cavity floor). The samples were cultivated in anaerobic conditions on solid pH-selective agar media of different acidity. Key findings: Each investigated lesion harbored a unique microbiota, both in terms of species composition and numbers of microorganisms. This indicate that various combinations of aciduric microorganisms can colonize, survive in and probably also propagate dentine carious lesions. We also found that solid pH-selective agars successfully can be used to select acid tolerant microorganisms in caries lesions. This would preserve their phenotypic traits for further study. In Paper III, the relation between salivary levels of matrix metalloproteinase-8 (MMP-8), salivary levels of tissue inhibitor of MMP (TIMP-1) and presence of manifest caries lesions in a large number of subjects was investigated. Saliva samples were collected and analyzed for concentrations of MMP-8, TIMP-1 and total protein using immunofluorometric assay, enzyme linked immunosorbent assay and Bradford assay, respectively. Key findings: Subjects with manifest caries lesions had significantly elevated levels of salivary MMP-8 compared to subjects without caries lesions. TIMP-1 was not significant in any case. In Paper IV, a new method for generating bioactive demineralized dentine matrix substrate (DDM) was developed, using a dialysis system and two different demineralization approaches (acetic acid (AA) or EDTA). The generated DDM was subsequently analyzed for presence of type 1 collagen, active MMP-8 and hydroxyproline (HYP) levels using SDS-PAGE, ELISA or immunofluorescence assay. Key findings: Both demineralization methods produced a substrate rich in collagen and with preserved MMP-8 activity. The report presents new knowledge on the composition of the acid tolerant dentine caries microbiota from three levels in dentine carious lesions and on the efficacy of operative caries removal on the numbers of viable microorganisms in the caries free cavity using two different operative methods. Moreover, the basic mechanisms behind collagen degradation in the dentine caries process are studied from both a clinical and laboratory perspective. The report provides a reference for further studies on dentine caries microbiology and dentine caries collagen degradation mechanisms, both of which are only known in part.

Place, publisher, year, edition, pages
Malmö University, Faculty of Odontology, 2014. p. 94
Series
Swedish Dental Journal : Supplement, ISSN 0348-6672 ; 233
Keywords
Dental Caries, Collagen, Cariogenic Agents
National Category
Dentistry
Identifiers
urn:nbn:se:mau:diva-7685 (URN)17596 (Local ID)978-91-7104-398-6 (ISBN)9789171043979 (ISBN)17596 (Archive number)17596 (OAI)
Note

Note: The papers are not included in the fulltext online.

Paper IV in dissertation as manuscript.

Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2024-03-14Bibliographically approved

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Hedenbjörk-Lager, AndersÅkerman, SigvardEricson, Dan

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