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Title: Integrin-dependent regulation of proteoglycan synthesis in cultured human articular chondrocytes following mechanical stimulation
Author: Holledge, Masumi Maruo
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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The aim of my thesis was to investigate the effects of cyclical mechanical stimulation on proteoglycan (PG) metabolism in chondrocytes derived from patients with OA and RA, in comparison with that of chondrocytes from normal cartilage. The chondrocytes were exposed to cyclical mechanical stimulation in an apparatus that functioned to produce a strain on the base of the culture dishes with attached cells in monolayer. Following 20 minute 4000m strain cyclical mechanical stimulation at 0.33 Hz, the GAG synthesis of chondrocytes from normal cartilage (measured by the DMMB assay) increased significantly compared to unstimulated controls. Increased GAG synthesis following mechanical stimulation was blocked in the presence of antibodies to a5 integrin, or aVb5 integrin, or CD47. These experiments provided evidence that a5 integrin, aVb5 integrin, and CD47 are involved in the signal transduction process that leads to accelerated PG synthesis, following cyclical deformation of chondrocytes from normal cartilage. Cyclical mechanical stimulation applied to articular chondrocytes from patients with OA and RA in monolayer culture did not show any significant change in GAG synthesis, measured by the DMMB assay. Chondrocytes from OA grade III synthesized on average 65.0 per cent and 59.6 per cent less GAG (corrected by DNA) than OA grade I and II chondrocytes, which were statistically significant (p=0.0038 and p=0.071 respectively). OA grade III chondrocytes showed a lack of the synthesis of large molecular weight aggrecan core protein with a molecular weight of around 350 kDa. The apparent intensity of the large molecular weight 350 KDa band increased following the mechanical stimulation of OA grade I and II chondrocytes in the presence of anti-a5 integrin antibody.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available