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Title: The effects of mechanical stimulation on proteoglycan synthesis by articular chondrocytes
Author: Bavington, Charles D.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The aim of this thesis was to investigate the effects of cyclical mechanical stimulation on chondrocyte proteoglycan (PG) metabolism and to explore the mechanisms involved in the transduction of the mechanical stimulus into a biochemical response. Chondrocytes were exposed to cyclical pressurisation in an apparatus that functions to produce strain of the base of culture dishes with deformation of attached cells. PG synthesis during pressurisation, was increased significantly compared to controls following 6 h and 3 h cyclical pressure-induced strain (PIS). These experiments provided the first evidence that stretch-activated ion channels are involved in the signal transduction process that leads to accelerated PG synthesis following cyclical deformation of chondrocytes. Two antibodies (3B3 and 7D4) raised against epitopes within the chondroitin sulphate chains of cartilage PG have been shown to be of particular value in detecting structural changes early in the development of OA. Methods were established for the measurement of these epitopes and normal chondrocyte glycosaminoglycan (GAG) epitopes by flow cytometry. 3B3 and 7D4 epitopes were expressed at low levels in both human and bovine chondrocytes from normal tissue. There was no increase in their expression up to 24 h after stimulation of chondroytes for 3 h with cyclical PIS. A new apparatus was developed for the production of cyclical PIS, which could accommodate two strained and two unstrained dishes under conditions of pressurisation. This apparatus proved suitable for further studies of the signal transduction mechanisms involved in responses to PIS. Chondrocytes treated with adhesion-blocking anti-α5 and anti-β1 integrin antibodies had a reduced response to strain, whereas those treated with an adhesion enhancing anti-β1 integrin antibody results in an increased response. These results implicit α5β1 integrin, which is the cell surface receptor for fibronectin, as a mechanotransducer in chondrocytes. The studies demonstrate that chondrocytes respond to cyclical deformation by increasing PG synthesis but that the expression of GAG-epitopes associated with OA was not increased.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available