Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659275
Title: Altered biological responsiveness of cells regulating intramembraneous bone repair associated with Type 2 Diabetes Mellitus
Author: Yusop, Norhayati
ISNI:       0000 0004 5359 8966
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2015
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Abstract:
The successful outcome from implant procedure relies heavily on the integration between the implant and the surrounding bone tissues. Besides, Type 2 Diabetes Mellitus (T2DM), which is linked with delay of osseointegration and reduction of bone-implant interface, further compromises the success rate of implant in diabetic patients. Apart from hyperglycaemia, the precise mechanism of diabetes influence on bone repair associated with dental implants is not completely understood. Nevertheless, the transforming growth factor-β1 (TGF-β1) has been indicated to increase healing processes, by exerting the stimulatory role on mesenchymal stem cells (MSCs) and macrophage populations during the inflammatory stage of bone repair. Moreover, the bioavailability of growth factors has been associated with the functional role of SLRPs, particularly biglycan and decorin. However, the responsiveness of each relevant bone-repair cell and biomolecule during bone repair in a diabetic environment has not been fully evaluated. On the other hand, the in vivo osseointegration of implant in T2DM animal models,investigated in respect to the expression of TGF-β1 by MSCs, demonstrated statistically significant differences in TGF-β1 labelled between the young diabetic and the control groups. Besides, the in vitro assessment demonstrated alterations for TGF-β1 expression and synthesis by osteoprogenitor cells, macrophages populations,between cells with different proliferative states, and prior hyperglycaemic-induction. Moreover, hyperglycaemia altered osteogenic and adipogenic differentiation capacities in MSCs. The data also suggested that hyperglycaemia induced lower proliferative capacity in MSCs, which led to significant changes in growth factor and proteoglycans bioactivity in bone repair. Hence, the data gathered from both in vivo and in vitro experiments suggested the potential association of MSCs proliferative stage with bioavailability of TGF-β1 and proteoglycans sequestration in the extracellular matrix compartment. Apart from that, the inter-dependent relationship observed between the osseointegration biomolecules directly exerted a synergical impact on the capability of MSCs to form osteoblast and further stimulate bone formation in order to induce bone-healing processes. Thus, the original contribution of this study to the field of reparative medicine is the novel identification and the characterisation of key biological components in both cellular and molecular bone repairs; the osteoprogenitor cell populations, as well as the macrophages, in relation to hyperglycaemia that directly influences growth factors, signalling the role of proteoglycans during the bone repair processes in T2DM. Collectively, the evidence gathered within this study is highly valuable to assist in elucidating the relevant therapeutic target to accelerate bone repair processes in T2DM patients. Keywords: diabetes, osseointegration, hyperglycaemia, bone, growth factors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.659275  DOI: Not available
Keywords: RK Dentistry
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