Grant: Operating Grant

Osteoarthritis (OA) is commonly described by joint pain and reduced joint movement associated with narrowing of joint space, cartilage destruction and changes in bone formation. It is a leading cause of disability in Canada with economic expenses close to $22 billion in Canada. With increasing life expectancy, OA is a major clinical concern. Despite extensive research, the mechanisms by which OA can be stopped remains to be determined. Our animal and cell based studies suggest that PPARgamma (a biological factor) is an attractive target for the treatment of OA. Activation of this biological factor by certain drugs such as rosiglitazone (FDA approved anti-diabetic drug) has been shown to reduce inflammation and symptoms related to OA in animal models. However, one of the key problems of these drugs is that they activate not only PPARgamma but also other variety of factors resulting in serious side effects in patients such as heart attack and stroke. Since these drugs activate other factors, the exact role of PPARgamma in cartilage development and in OA is unknown. Therefore, this study for the first time will investigate the specific role of PPARgamma in cartilage development and OA using mice in which PPARgamma is genetically absent only in the cartilage and then we will compare mice data to cartilage samples collected from normal human and OA patients and specifically answer the following questions: (1) Does PPARgamma control growth and development of the cartilage? (2) Does PPARgamma control cartilage damage observed during OA? (3) Does PPARgamma inhibit inflammation and production of harmful mediators which destroy the bone and cartilage during OA? I anticipate that this study will show that PPARgamma is the key target likely to control inflammation and damage to bone and cartilage observed in OA. Therefore, this project has the potential to generate new therapeutic strategies for the treatment of OA and other forms of arthritis such as rheumatoid arthritis.