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Abstract
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 nonfunctional 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.