Furthering knowledge of the pathogenesis of periodontal disease in the evaluation of biomarkers for monitoring disease susceptibility and activity

Koshy, Bindhu 2015. Furthering knowledge of the pathogenesis of periodontal disease in the evaluation of biomarkers for monitoring disease susceptibility and activity. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

Summary The development of periodontitis is a multifactorial process initiated by a bacterial-induced inflammation which is further modified by genetic and environmental factors contributing towards an exaggerated host response and associated tissue destruction. Pro-inflammatory mediators such as cytokines play an important role in the resulting inflammation leading to degradation of periodontal connective tissue, several of which may be detected in GCF and may be of diagnostic and prognostic value. However, our limited understanding of the molecular mechanisms involved in the pathogenesis of periodontal disease restrains the effectiveness of current diagnostic and management techniques in assessing true periodontal health, identify susceptible patients, monitor response to therapy or implement the use of biomarkers which may assist in the management of patients with periodontal disease. Therefore, this thesis aims to further our understanding of the pathology of periodontal disease through a series of in-vitro and in-vivo studies. In recognising that as a consequence of periodontal disease is the degradation of the extracellular matrix, clinical studies investigated the release of proteoglycan components from the periodontal tissue in patients with chronic periodontitis. Increasing levels of chondroitin sulphate (CS), a proteoglycan metabolite was observed with progressive clinical attachment loss, highlighted periods of activity and inactivity, with only a few sites demonstrating disease activity over a 21 month period. Furthermore, in-vitro studies investigated the cellular synthesis of proteoglycan in a pathological condition by examining the biological effects of P. gingivalis LPS on PDL cells. In the presence of P. gingivalis LPS, an alteration in cell behaviour was observed with an increase in cell proliferation and a decrease in matrix formation, further suggesting that the degradation products detected in GCF such as decorin and biglycan, were as a consequence of tissue destruction and not as a result of repair or remodelling. Collectively, these results highlight the potential of CS present in GCF as a marker of disease activity. Due to the multifactorial nature of the disease, it is highly unlikely that any one marker may provide information that may be of diagnostic as well as prognostic value. Rather, the use of iv a panel of markers may further corroborate the implementation of biomarkers in periodontal disease management. Therefore, in considering the prominent role of cytokines in tissue destruction, this thesis further examined the prognostic value of cytokine profiling in identifying the high risk patient. On cross-sectional evaluation of cytokine profiles in GCF from patients with different types of periodontal disease using bead array technology, a variable response was observed in the severe type, which was suggestive of an imbalance in Th1/Th2/Th17/Treg responses, further affirming the predominant role of an altered host response in disease progression. Further, resident PDL cells were also considered as potential contributors to the variation in response. Consequently, in-vitro studies demonstrated that although TLR receptors were present on PDL cells, no cytokines were released on exposure to P. gingivalis LPS further suggesting that the cytokines detected in GCF were produced as a consequence of an altered host response which brings about progression of disease. In conclusion, the development of rapid, non-invasive, site based risk assessment and comprehensive screening for biomarkers may be possible in the near future as a result of the rapid development of new diagnostic technologies such as microarray and microfluidics along with the use of oral fluids such as GCF. Therefore, in the future enhanced patient assessment may be possible which will enable provision of customized therapies that target treatment at individual level.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Dentistry
Subjects:	R Medicine > RK Dentistry
Uncontrolled Keywords:	periodontal diseases; biomarkers; cytokines; chondroitin sulphate; p.gingivalis LPS, periodontal ligament cells.
Date of First Compliant Deposit:	30 March 2016
Last Modified:	20 Dec 2023 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/86804

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