Principal Investigator Alan Grodzinsky
Joint injury caused by mechanical overload in vivo results in acute damage to cartilage and surrounding joint tissues. An inflammatory response accompanies acute injury, characterized by increased levels of pro-inflammatory cytokines in the synovial fluid (e.g., IL-1, IL-6, TNF-α) as well as increased levels of extracellular matrix fragments. Injury and prolonged inflammatory insult significantly increases the risk of developing arthritis. We have developed in vitro models that emulate injury to the whole joint, including incubation of injured cartilage in the presence of exogenous cytokines, and co-culture of injured cartilage in the presence of synovial tissue explants which secrete catabolic factors that can act on cartilage. Collaborations with the pharma and biotech industries are aimed at testing the hypotheses that (1) cartilage mechanical injury in the presence of inflammatory factors results in a synergistic degradation of cartilage matrix, and (2) that selected pro-anabolic and anti-catabolic treatments (e.g., small molecule enzyme inhibitors and biologic (antibody) cytokine blockers) can ameliorate cartilage degradation. A multi-targeted systems biology approach is used to studying fundamental mechanisms underlying tissue degradation. In parallel, we are initiating tests of this approach using mouse mimics of injury in vivo.