Osteoarthritis (OA) is the most prevalent form of arthritis in the world. A number of potential disease-modifying drugs are under evaluation, but to date there is little evidence of significant efficacy. Current therapies are focused on providing symptomatic relief rather than halting disease progression. It is estimated that by 2030, 25% of adults aged 18 years and older will have doctor-diagnosed arthritis. Furthermore, the number of individuals requiring replacement surgery is predicted to rise to 4 million annually worldwide. As a result, a number of studies are underway to identify new therapeutic targets/approaches to treat or prevent joint-destruction in OA. Dysregulated immune-cell metabolism has been linked to a number of debilitating diseases, including arthritis, and it has been strongly suggested that inhibiting inflammation caused by OA synovial cells represents a novel approach to regulate joint function and promote cartilage repair. However, the effects of therapeutically altering metabolic pathways requires extensive investigation prior to clinical testing. We propose to contribute to this emerging field of research by determining if the inhibition of cartilage formation by factors of the disease which are produced by immune-cells can be reversed with the use of metabolic inhibitors. We will also determine if metabolic changes impact on the fate of mesenchymal stem cells and whether this can be manipulated to promote favourable bone and cartilage formation. Our ultimate goal is to provide new insights into the pathophysiology of OA and to contribute to the development of novel therapeutic strategies for OA treatment.