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Title: The role of Wnt signalling pathway in mechanotransduction pathway in SV-40 immortalised human chondrocyte cell lines
Author: Afsari, Farinaz
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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This thesis has set out to investigate whether Wnt pathway components are expressed in human chondrocyte cell lines and to explore whether the Wnt pathway is involved in mechanotransduction in chondrocytes. For the first time it is demonstrated that the Wnt signalling components, Wnt-1, Fz-2, Fzrp and β catenin are expressed in human chondocyte cell lines. Fibronectin and CD44 are identified in association with chondrocyte Wnt-Fz complexes suggesting that they may be coreceptors necessary for transducing Wnt signals intracellularly. The formation of GSK3β/β catenin degradation complexes was induced by a Wnt agonist and delayed by mechanical stimulation of chondrocytes, while, induction of GSK3β activity by mechanical stimulation was inhibited by a PI3K inhibitor. These experiments suggest that the Wnt signalling pathway may be involved in mechanical signalling in these cells. However, the induction of the GSK3β activity following mechanical stimulation is mediated by a PI3K dependent pathway rather than the Wnt pathway. The activity of GSK3β and the formation of GSK3β/β catenin complexes in chondrocytes are influenced by an interaction between mechanotransduction and the Wnt signalling. These, in turn, control the cytoplasmic/nuclear distribution of β-catenin which affects the regulation of downstream target genes such ad CD44, fibronectin and some metalloproteinases. CD44 and fibronectin are essential components of cartilage, which are involved in matrix assembly and the maintenance of cartilage integrity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available