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Effects of mechanical strain hyaluronan metabolism of synovial cells from osteoarthritic knees

Williams, Rebecca 2004. Effects of mechanical strain hyaluronan metabolism of synovial cells from osteoarthritic knees. PhD Thesis, Cardiff University.

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Development of the synovial joint is complex involving a sequence of precisely controlled events. Separation of the cartilage anlagen involves differential matrix turnover and requires mechanical stimuli, the loss of mechanical stimuli results in joint fusion. Synthesis of hyaluronan at the developing joint line occurs and its continued synthesis is necessary for maintenance of frictionless movement in the adult joint. Hyaluronan is synthesised by synovial fibroblasts and as a component of the synovial fluid and synovium, helps maintain a consistent volume and viscosity of synovial fluid when the joint is flexed. Reduction in hyaluronan concentration within the synovial fluid is associated with osteoarthritis and rheumatoid arthritis. Joints become painful to move and nihility is lost. The study aimed to investigate whether synovial cells from osteoarthritic knees were able to respond to mechanical stimuli and if so, were cells able to modulate hyaluronan synthesis. Results at the cellular level would be the first step in considering exercise based therapies as a treatment for osteoarthritis. A four point bending mechanical loading jig was used to apply mechanical strain to synovial cells. Results indicate that synovial cells from osteoarthritic knees are capable of responding to a brief period of mechanical stimuli and modulate hyaluronan release. Differential expression of the three HAS genes was also observed upon mechanical strain. It was clear however, that the response to strain varied depending on cell passage. As a result, the development of an immortalised synovial cell line was investigated. Data obtained however, showed that ectopic hTERT expression alone was not sufficient to immortalise synovial cells. Development of exercise based therapies for the treatment of osteoarthritis will require a considerable amount of further work. This study however, has demonstrated that alterations in hyaluronan synthase expression and subsequent hyaluronan synthesis by synovial cells occurs upon mechanical stimuli and thus provides a foundation for future studies.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
ISBN: 9781303201011
Date of First Compliant Deposit: 30 March 2016
Last Modified: 08 May 2014 10:42

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