Gingival Crevicular Matrix Metalloproteinases and Their Inhibitor in Health, Disease and Treated Periodontitis

Haerian-Ardakani, Ahmad (1994) Gingival Crevicular Matrix Metalloproteinases and Their Inhibitor in Health, Disease and Treated Periodontitis. PhD thesis, University of Glasgow.

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Abstract

Proteinases have long been implicated in the pathogenesis of periodontal disease. Matrix metalloproteinases (MMPs) are a family of enzymes thought to be involved in periodontal tissue breakdown as well as tissue remodelling. MMPs are capable of degrading a variety of extracellular matrix components. Among these enzymes polymorphonuclear leucocyte derived collagenase (PMN-CL) and fibroblast derived collagenases (FIB-CL) have the unique ability to degrade type I, II and III collagens across the triple helix of the collagen fibre. Tissue inhibitor of metalloproteinases (TIMP), which are locally produced by host cells, inhibit these proteinases. TIMP appears to preferentially inhibit FIB-CL and stromelysin (SL). Most of the cells which produced FIB-CL and SL, also produce TIMP. No studies have so far been conducted on fibroblast derived MMPs and TIMP in gingival crevicular fluid (GCF). These experiments were carried out to investigate the GCF levels of FIB-CL, SL and TIMP in relation to periodontal disease status. GCF samples were collected by means of sterile paper strips inserted into the crevice until mild resistance was felt and left for 30 seconds. GCF volume was assessed using the Periotron 6000. The enzymes and inhibitor levels were assayed using modifications of sandwich ELISAs described by Cooksley et al. (1990). Antibodies detected both active and latent MMPs and the free form of TIMP. The results were expressed as absolute amounts i.e. pg/30 seconds of sample collection. Using these methods, it was possible to assess all three GCF proteins in the same sample (paper strip). The clinical studies conducted in this thesis are; a) a cross-sectional study of matrix metalloproteinases and their inhibitor and b) a longitudinal study of matrix metalloproteinases and their inhibitor before and after treatment. The cross-sectional study was carried out to test the ability of GCF levels of FIB-CL, SL and TIMP to distinguish healthy, gingivitis and periodontitis sites. GCF samples were collected from forty patients, each provided three samples from healthy, gingivitis and periodontitis sites. The mean GCF levels (pg/30s) of SL and TIMP were significantly higher in diseased (gingivitis and periodontitis) when compared to healthy sites. Both the enzyme and inhibitor failed to differentiate gingivitis from periodontitis. SL and TIMP demonstrated moderate correlation with clinical parameters when pooled data from three categories of sites were used. FIB-CL reached the detectable level of the assay in only 20.8% of the sites and did not demonstrate association with disease status. The aim of the longitudinal study was to investigate the effects of periodontal therapy on the GCF levels of FIB-CL, SL and TIMP as well as the ability of the baseline levels of these proteins to predict the outcome of treatment. Twenty one patients with advanced periodontal disease, each providing 8 GCF samples, comprised the study population. GCF sampling and clinical recordings were performed at three time points namely, baseline (before treatment), reassessment (after hygiene phase therapy (HPT)) and at the follow-up (after additional therapy) examinations. Attachment level (AL) and pocket depth (PD) were measured using the "Florida probe". All patients received oral hygiene instruction, scaling and root planing. Further treatment needs were determined based on the pocket depths and the state of bleeding on probing (BOP) six weeks after HPT, at the reassessment visit. Follow-up examination was performed at least six weeks after additional therapy. Clinical parameters were reduced at both post therapy visits, while the mean level of SL decreased after HPT, TIMP level increased at this visit. Both proteins showed significant reduction at the follow-up visit. When sites were grouped according to their response to treatment, using different criteria i.e. PD, BOP and AL, this pattern of change was observed in all groups of sites which did or did not respond to treatment. The percentage of sites with detectable amounts of FIB-CL was 26.8%, 17.4% and 12% at three successive visits respectively. Baseline GCF levels of MMPs and TIMP failed to predict the outcome of treatment. The association between clinical and biochemical parameters were investigated in several situations. Of these, SL and TIMP demonstrated significant and positive correlation with GCF volume only in the group of sites which gained attachment after therapy. As FIB-CL was detected in very small number of sites, no attempt was made to correlate its level with the clinical parameters. The failure of SL and TIMP to distinguish gingivitis from periodontitis sites could be due to the fact that probing depths served as a differentiating factor between these groups of sites, keeping in mind that probing depth measurements taken at one point in time do not necessarily reflect active periodontal destruction. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: D F Kinane
Keywords: Dentistry
Date of Award: 1994
Depositing User: Enlighten Team
Unique ID: glathesis:1994-74820
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Nov 2019 15:58
Last Modified: 13 Nov 2019 15:58
URI: https://theses.gla.ac.uk/id/eprint/74820

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