SignificanceCartilage mineralization is imperative in various processes such as skeletal growth and fracture repair. However, this process may also be pathological, as in the case of the degenerative joint disease, osteoarthritis (OA). Using a posttraumatic OA model (PTOA), we find that cartilage-specific genetic nulls caused severe synovitis and mineralization of the lateral joint compartment, due to augmented gene expression. Conversely, cartilage-specific nulls exhibited impaired synovitis and mineralization of the lateral joint, accompanied by a reduction of local pain. Consistently, transcriptomic profiles of -ablated chondrocytes exhibited enhanced anabolism, yet impaired pathways related to calcification and inflammation. Accordingly, cartilage mineralization of the lateral joint compartment relies on amplified inflammatory pathways, contributing to articular damage following PTOA.