Besides, HMGB1 levels in synovial fluid reflects the severity of OA.34 High‐mobility group box 1 can synergize with IL‐1β to amplify the inflammatory response, resulting in the production of a large number of cytokines, chemokines, and MMPs.10 We thus suspect that CCN3 may protect against osteoarthritis via HMGB1 modulation. This evidence concerns the gene HMGB1 and osteoarthritis.