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Title: Altered bone cell biology associated with Type Two Diabetes Mellitus : consequences for periodontal disease
Author: Al-Qarakhli, Ahmed
ISNI:       0000 0004 7426 6493
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2018
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Periodontitis is a widely spread disease, affecting about 80% of the worldwide population, resulting in teeth loss, a heavy impact on patients in terms of function and aesthetic. Type 2 Diabetes Mellitus (T2DM) is described to be linked to the exacerbation of periodontitis and delayed healing. This link between these two diseases, however, is not fully evaluated and the mechanisms are yet to be fully elucidated. Osteopontin (OPN) is described to inhibit mineral crystal formation. Herein, it has been hypothesized that increased OPN in diabetic healing bone may be the causative factor of delayed healing in periodontitis and subsequent deterioration, leading to teeth loss. This project aims to gain a greater understanding of the effect of high glucose (HG) levels on mesenchymal stem cells (MSCs) and macrophages, their ability to synthesise OPN and hence, its effects on MSCs to synthesise new bone tissue. Further, the influence of Porphyromonas gingivalis lipopolysaccharides (Pg-LPS) on these cells was analyzed, in an attempt to create a model to study the healing in the presence of periodontitis and T2DM. Investigating the MSCs isolated from the rat compact bone (CB-MSCs) during the growth in culture, revealed two main populations; a heterogenous population appeared with predominantly mature characteristics at PD15. This population then demonstrated a change in its heterogeneity and became more immature in nature at PD50. These two main populations differed in their growth rate and capability of osteodifferentiation. HG environments exerted significant decreases in osteogenic differentiation on PD15, but not PD50. Addition of pg-LPS showed inhibitory effects on osteodifferentiation on PD15 cells more than PD50. Conversely, in the combined presence of HG and pg-LPS, PD50 showed a significant decrease in osteodifferentiation. OPN levels demonstrated a gradual decrease in CB-MSCs in both normal and HG conditions. Investigating OPN levels secreted by macrophages, however, revealed interesting results. Synergistic effects of both HG and pg-LPS exhibited a significant increase in OPN levels in both pro-inflammatory M1 macrophages and in repair related M2 macrophages. In conclusion, HG was mainly reported to inhibit osteogenic differentiation of the mature cell population, whereas the immature population was found to be affected by combined pg-LPS and HG. OPN levels in HG conditions were shown to decrease along the osteodifferentiation period. However, macrophages showed increase secretion of OPN by the synergistic effects of both pg-LPS and HG in both M1 and M2 and by pg-LPS effects in M2 macrophages. These outcomes as far as we are aware, are novel and disclose a new mechanism of bone resorption in the case of T2DM patients concurrently with periodontal disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General) ; RK Dentistry