2 Imbalance of Prevalence and Specialty Care for First Nations with Osteoarthritis in

Objective: The main cause of lethality in the autoimmune connective tissue disease scleroderma is organ fibrosis. Cellular behavior is altered by their local microenvironment, which includes enhanced local stimulation of mechanical signaling pathways. Fibrotic lesions are, by their nature, characterized by significantly enhanced mechanical forces relative to healthy tissue. Previous evidence from our laboratory has identifed the myofibroblast (a highly adhesive and contractile fibroblast that exerts mechanical tension on surrounding tissue) as the critical effector cell in the fibrosis observed in scleroderma. This observation led us to test the hypothesis that enhanced mechanosignaling was required for fibrogenesis. The signaling receptors required for mechanotransduction are the integrins, and we have previously shown that a neutralizing antibody to integrin beta 1 reverses the fibrotic phenotype of lesional scleroderma fibroblasts and that integrin beta 1 knockout mice are resistant to bleomycin-induced skin fibrosis.