UTILITY OF ACTIVE MMP-8 AS A TEST BIOMARKER IN PERIODONTAL AND PERI-IMPLANT DISEASES: DIAGNOSIS, PREVENTION AND TREATMENT OUTCOMES

Abstract

Active matrix metalloproteinase (aMMP-8), collagenase-2, is a key mediator in the destruction of tissues seen in periodontitis and peri-implantitis. It can be detected in oral fluid samples, including gingival crevicular fluid (GCF), saliva, mouth rinse and peri-im- plant sulcular fluid (PISF). Active MMP-8, which is mainly expressed by neutrophils, can degrade almost all extracellular matrix and basement membrane components; it is causes particularly high levels of degradation in type I collagen, which is present in periodontal ligaments. In the first part of this thesis, we demonstrated that during an experimental gingivitis study aMMP-8 was not detectable in saliva. Therefore, this study confirms the evidence; aMMP-8 is detected in periodontitis. Simultaneously, the lateral-flow chairside aMMP-8 immuno- tests, PerioSafe and ImplantSafe with the Oralyzer reader, which are based on Professor Timo Sorsa’s research, were introduced and validated to analyse the levels of aMMP-8 in mouth rinse or PISF. Thus, the last parts of the thesis evaluate the accuracy and reliability of these developed tools: PerioSafe and ImplantSafe/Oralyzer, and whether they could provide an easy-to-use and quick way of identifying periodontitis and peri-implantitis. Our results indicated that the tools were successful in their detection. They were also very accurate in terms of both sensitivity and specificity with clinical periodontal parameters, such as bleeding on probing (BOP) and plaque index (PI). In addition, study V has inves- tigated the effectiveness of sub-antimicrobial doses of doxycycline (SDD) treatment when combined with non-surgical periodontal therapy, and their effect on potential GCF bio- markers in periodontal tissue destruction over a period of twelve months. The analysed biomarkers were MMP-8, -9, -13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase 5 (TRAP-5), which were determined by various immu- nofluorometric analyses (IFMA) and enzyme-linked immunosorbent assays (ELISAs). The results demonstrated reduced GCF levels in two MMPs that most commonly associated with periodontitis; MMP-8 and -9, and MPO, which potentially causes oxidative activation in them. However, MMP-13 and TRAP-5 could be detected in the relevant GCF samples, whereas the OPG levels also decreased significantly as a result of adjunctive SDD therapy. This thesis showed the reliability of these tools, PerioSafe and ImplantSafe/Oralyzer, for the successful detection, prediction and monitoring of the progress of periodontitis and peri-implantitis, and their response to treatment. Additionally, we delved further in to the beneficial effects of sub-antimicrobial doses of doxycycline therapy.