Grant: Operating Grant

Osteoarthritis (OA) is the most prevalent form of arthritis and the leading cause of disability in Canada and the rest of the world. The impact of this disease is expected to increase dramatically as a result of increased life expectancy and population aging. OA is characterized by chronic pain, cartilage degradation and loss of function. These processes are due to increased production of several inflammatory and catabolic mediators. So far, there is no efficient treatment for OA. We have demonstrated for the first time that PPARgamma activators inhibited several inflammatory and catabolic responses in vitro and were protective in animal models of the disease. We have also demonstrated that the L-PGDS products have anti-arthritic effects in vitro. In this project we will utilize different approaches to characterize the pattern of PPARg expression during OA and to define the role of L-PGDS in animal models of the disease. With regard to PPARg expression, we will analyse the role of DNA methylation in the regulation of this gene expression. With regard to L-PGDS, we will investigate the course of OA in L-PGDS deficient mice These studies will improve our understanding of the pathogenesis of OA and will be very helpful in developing more efficient therapeutic strategies for the treatment of OA and possibly other arthritic diseases.