Grant: Operating Grant: Fall 2008 Priority Announcement (IMHA)

Musculoskeletal diseases represent the largest burden to the health care system and are major contributors to long-term disability and reduced quality of life. Of this group of diseases, degenerative joint diseases (DJD) such as osteoarthritis (OA) makes up the largest proportion. In Canada, 10-20 percent of the general population has OA, whereas, ~85 percent of people over 65 exhibit signs of OA. OA is primarily characterized by deficiencies in joint cartilage and potentially underlying bone, that contribute to a loss of joint mobility and pain. At present, there is no cure for OA, severely affected load-bearing joints are partially or completed replaced with artificial ones. The underlying processes that contribute to the initiation and/or progression of OA are poorly understood. The retinoids, derivatives of Vitamin A, are potent modulators of chondrocyte behaviour and in recent studies we have discovered that genes regulated by retinoids are substantially increased in animal models of OA. This proposal will test the role of retinoids in OA, but will also investigate the ability of antagonists of this pathway to reverse or slow the progression of OA.