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Title: Extracellular matrix changes in degenerated and painful intervertebral discs
Author: Al-Abbasi, Maan Majid Salih
ISNI:       0000 0004 2717 2785
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Intervertebral disc degeneration (IVDD) remains one of the commonest causes of chronic disability in the working years. It involves both structural disruption and cell mediated alteration in the extracellular matrix (ECM) composition of the disc. ECM changes differentiation between disc degeneration and the normal physiological ageing and between disrupted and non-disrupted discs is also not fully understood. The hypothesis of this dissertation, is that IVDD is initiated by micro-damage to disc tissues, followed by cellular attempts to repair which are impeded by some degree of tissue hypoxia, leading to synthesis of an "inferior collagen" and to progressive disc degeneration. The collagen turnover of the extracellular matrix in aged and degenerated as well as in disrupted and non-disrupted discs were determined by measuring the levels of proteolytic enzymes such as the matrix metalloproteinases (MMPs) and collagen cross links. Other ECM components such as sulphated glycosaminoglycans (sGAG) and water contents were also measured in both disc groups. The biochemical and thermal changes were compared in hypoxic and normoxic monolayer cell culture medium of cultured human fibroblasts. Aged discs were found to have greater level of matrix turnover associated with synthesis of poorly hydroxylated neo-collagen as well as different ECM composition, than degenerated discs which found to have increased level of MMPs that might facilitate cellular invasion into their disrupted matrix. Disrupted discs were found to have imbalanced collagen degradation (over synthesis) which might lead to a weak non- functional disc. Focal tissue disruption acquiesce swelling of tissue as well as GAG depletion, thus, altering the GAG/water ratio locally. Painful discs with structural disruption were found to have up-regulated MMPs which is thought to contribute to further annular weakening (radial annular tear) leading to the nuclear material to be forced outward (disc herniation) induced by trauma and/or axial load shift.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available