Grant: Operating Grant

More than 4 million Canadians have arthritis and the number of people living with arthritis has grown by 50% in the last ten years. Arthritis is responsible for 6% of hospital admissions in Canada and costs Canadians $6.4 billion/year in health care expenses and lost work days. Osteoarthritis is a subset of arthritis involving cartilage damage and bone sclerosis. Current treatments, such as anti-inflammatory drugs and joint replacement surgery, alleviate the symptoms (pain, compromised joint function) of osteoarthritis, but do not diminish its signs. A pressing need remains for joint localized therapies and interventions that could slow or ideally stop this debilitating disease. For this project, we will investigate the role of a collagen receptor found on cartilage cells - integrin alpha1beta1 - in the development and progression of osteoarthritis. Integrin alpha1beta1 is more pronounced on chondrocytes during the early stages of osteoarthritis and this likely protects against the disease. The mechanism whereby integrin alpha1beta1 may protect cartilage from osteoarthritis however is unclear. In this proposal we will investigate the interaction of integrin alpha1beta1 with two growth factor receptors on chondrocytes known to play important roles in osteoarthritis. We will use genetic mouse models of injury induced or spontaneous (with old age) knee osteoarthritis to determine how the interplay between integrin alpha1beta1 and these growth factor receptors plays a critical role in the development and progression of osteoarthritis. By advancing our understanding of the molecular underpinnings of osteoarthritis, and in particular the protection offered by integrin alpha1beta1 and its interaction with growth factor receptors against this disease, we hope to identify novel approaches for improved treatments that will ameliorate the lives of millions of Canadians.