Grant: Operating Grant

Osteoarthritis (OA) is the most frequent form of arthritis yet our capacity to treat OA is limited since we still do not know the causes of OA. In recent years, it became evident that OA cannot be limited to a disease of articular cartilage, although articular cartilage loss is the clinical hallmark of OA. We now know that multiple tissues are affect in OA and it is interesting to note that all tissues affected share a common precursor cell type, the mesenchymal stem cells (MSC) present in the bone marrow. These MSC can proliferate into a number of different cell types, namely osteoblasts (Ob), adipocytes (Adipo), and chondrocytes. Most importantly, the capacity to form Ob from bone marrow of OA patients is increased whereas the capacity to form Adipo or chondrocytes is reduced. MSC can form these multiple cells in response to local factors promoting one or the other cell type. In particular, the Wnt signaling pathway, a very important pathway for cell proliferation, differentiation and commitment to a specific lineage, is responsible to control the balance between Ob and Adipo in bone marrow. We recently reported that the Wnt signaling pathway is reduced in Ob from OA patients which could explain the altered capacity to form mature Ob and Adipo in OA patients. Indeed, local factors produced by Ob from OA patients inhibit the normal function of chondrocytes, hence could also influence the recruitment of MSC from the bone marrow. Our proposed studies will explore the role and impact of the Wnt signaling pathway in human OA MSC, and in mouse MSC from an animal model of OA to test new avenues of treatment to correct the altered mechanism that leads to abnormal recruitment and proliferation of Ob and Adipo from human OA MSC. This approach could then be translated into new clinical intervention in human OA.