Do the intrinsic properties of the chondrocytes account for the difference in prevalence of OA in the knee and ankle?

Miller, Andrew S. 2019. Do the intrinsic properties of the chondrocytes account for the difference in prevalence of OA in the knee and ankle? MD Thesis, Cardiff University. Item availability restricted.

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Abstract

Introduction The lifetime prevalence of symptomatic osteoarthritis (OA) in the knee is < 44% compared to 3.4-4.4% in the ankle. This has led to the theory that ankle articular cartilage must have some degree of inherent resistance to osteoarthritis (OA), although it is unknown whether this is attributed to biomechanical and/or biochemical differences. It has been previously hypothesised that biochemical differences in ankle cartilage extracellular matrix composition confers this resilience. Interestingly, previous studies have demonstrated that the ankle is also more resistant to pro-inflammatory cytokine mediated degeneration. Therefore, this thesis aimed to further characterise the response of human ankle and knee cartilage to pro-inflammatory cytokines, commonly found in OA, to elucidate whether this may account for the inherent difference in OA prevalence between these two different joints of origin. Methods Talar domes and femoral condyles donated by patients following amputation were harvested and full-depth articular cartilage explants cultured in the absence or presence of a combination of physiological ‘low’ and pathological ‘high’ concentrations of cytokines, namely Interleukin-1 alpha (IL-1α), Oncostatin M (OSM) and Tumour Necrosis Factor alpha (TNFα) over a short-term (7 days) or long-term (28 days) culture period. Media was assessed for sulphated glycosaminoglycan loss (sGAG), lactate dehydrogenase, synthesis of nitric oxide (NO) and prostaglandin E2 (PGE2) and synthesis and/or activation of the Matrix Metalloproteinases MMP-2 and 9. Results A significantly higher proportion of sGAG loss, increased production of PGE2 and NO, in addition to induction and activation of pro MMP-9 was observed for knee cartilage explants only; furthermore, significant differences between joints was independently observed following culture in ‘high’ concentration TNFα. Consistent patient specific heterogeneity was observed across all outcome measurements confirming the hypothesis that there is an ‘inflammatory osteoarthritic phenotype’.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Date of First Compliant Deposit:	21 July 2020
Last Modified:	31 Jul 2020 01:24
URI:	https://orca.cardiff.ac.uk/id/eprint/133633

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