Significance Mitogen-inducible gene 6 (Mig-6) was found to be an important factor in maintaining joint homeostasis, and its loss in mice results in the development of an osteoarthritis (OA)-like disorder in multiple synovial joints. However, it was unclear in what cells Mig-6 was expressed and what cells were causal for developing the OA-like phenotype. Here we report that Mig-6 is uniquely expressed in the cells surrounding entire surface of the synovial joint, including chondrocytes in the superficial zone of the articular cartilage and in the meniscus, and synovial lining cells. We found that although chondrocytes play a critical role in developing the OA-like disorder in the knees, other cell types are likely required for full development of the Mig-6–deficient joint phenotype.