Osteoarthritis Osteoarthritis (OA) is a debilitating degenerative joint disease affecting more than 20 million individuals in the United States alone and is characterized by an irreversible loss of articular cartilage within the synovial joints. During the onset of OA, the articular chondrocytes responsible for production of the articular cartilage matrix undergo phenotypic changes similar to those that growth plate chondrocytes undergo during terminal maturation. While genetic, mechanic, and metabolic factors all contribute to the development of OA, we are primarily interested in identification of genetic alterations that give rise to the disease. Using genetic mouse models and articular chondrocyte cultures, we are actively investigating the role of several signaling pathways in articular cartilage maintenance and the onset of OA. For example, while it is well established that loss of canonical TGF-β signaling leads to an OA-like phenotype, we are currently investigating the role of non-canonical TGF-β, or Tak1-mediated, signaling in this process.