Altered biological responsiveness of cells regulating intramembraneous bone repair associated with Type 2 Diabetes Mellitus

Yusop, Norhayati ORCID: https://orcid.org/0000-0002-2867-1290 2015. Altered biological responsiveness of cells regulating intramembraneous bone repair associated with Type 2 Diabetes Mellitus. PhD Thesis, Cardiff University. Item availability restricted.

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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.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Dentistry
Subjects:	R Medicine > RK Dentistry
Uncontrolled Keywords:	Diabetes; Osseointegration; Hyperglycaemia; Bone repair; Growth factors
Date of First Compliant Deposit:	30 March 2016
Last Modified:	28 Jul 2023 15:02
URI:	https://orca.cardiff.ac.uk/id/eprint/75468

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