Grant: Proof of Principle Program - Phase I

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) make 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, which contribute to a loss of joint mobility and pain. Joint cartilage covers the surface of the bones in the joint and provides a low-friction surface to allow joint mobility and protection of the bones. At present, there is no cure for OA, severely affected load-bearing joints such as the knee or hip are partially or completed replaced with artificial ones. The underlying processes that contribute to the initiation and/or progression of OA are poorly understood. Using a variety of approaches we have recently identified several drugs that promote cartilage formation and/or slow cartilage degradation in cultures of cells that make cartilage. Two of these compounds have been used in humans for the past > 50 years in analgesic applications, and we have discovered they also influence cartilage formation and degradation. The aim of this proposal is study if these molecules can promote cartilage formation and/or slow cartilage degradation in joints tissues collected from humans (following joint replacement surgery). Furthermore, these drugs will be evaluated in animal models of arthritis. In short, we are attempting to identify therapeutic targets that can be used to treat osteoarthritis.