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Role of matrix fragments and mechanical signals in the development of osteoarthritis (MOHE, Government of Malaysia).

Principal investigator: E. Parker
Co-investigator(s): R. Tilwani, B Pinguaan-Murphy, G.A. Homandberg, and Tina CHOWDHURY

This application examines the competing pathways activated by the fibronectin fragments and dynamic compression. We believe that fibronectin fragments mediate cartilage breakdown through the induction of catabolic signalling cascades and are therefore, potentially the cause of the early damaging effects in osteoarthritis. More specifically, fibronectin fragments stimulate a nitric oxide driven matrix metalloproteinase-dependent pathway mediated by the activation of the MAP kinases and transcription factors. In contrast, the application of physiological levels of dynamic compression to chondrocytes blocks the catabolic pathways and initiates anabolic, reparative events . Cross talk threfore occurs between the specific pathways activated in response to both the fibronectin fragments and dynamic compression. In addition, the levels of oxygen tension in the injured joint will have a significant impact on the metabolic processes thereby affecting the maintenance of fragment-induced pathway. The interactions between matrix fragments, oxygen tension and mechanical loading are therefore complex, and thus motivates the current investigation. An understanding of the pathways will help to provide a focus for the development of safe targets for pharmacological and biophysical therapies and provide key parameters for integrated physiotherapeutic strategies for OA treatments.

The project supports Dr Eleanor Parker (PDRA) and Reshma Tilwani (PhD student). The work is funded by the Ministry of Higher Education, Government of Malaysia, High Impact Research Fund (UM.C/HIR/MOHE/ENG/44) in collaboration with Dr Belinda Pinguaan-Murphy.