Neural Cell Adhesion Molecule Regulates Chondrocyte Hypertrophy in Chondrogenic Differentiation and Experimental Osteoarthritis

Chondrocyte hypertrophy-like change is an important pathological process of osteoarthritis (OA), but the mechanism remains largely unknown. Neural cell adhesion molecule (NCAM) is highly expressed and participate the chondrocyte differentiation of mesenchymal stem cells (MSCs). In this study, we found that NCAM deficiency leads to hypertrophic chondrocyte differentiation in murine MSCs, in which extracellular signal-regulated kinase (ERK) signaling play an important role. Moreover, in an interleukin (IL)-1β induced OA cellular model, NCAM expression is down-regulated. Interestingly, overexpression of NCAM substantially inhibits hypertrophic differentiation in the OA cellular model. Consistently, NCAM deficiency accelerates chondrocyte hypertrophy in growth-plate and articular cartilage of OA mice. In conclusion, NCAM could inhibit hypertrophic chondrocyte differentiation of MSCs by activating ERK signaling and reduce chondrocyte hypertrophy in experimental OA model, suggesting the potential utility of NCAM as a novel therapeutic target for alleviating chondrocyte hypertrophy of OA. Funding Statement: This work was supported by the grants from the National Natural Science Foundation of China (No. 81403161, U1704186, 81402416 and U1404816), Key Scientific Research Project of Colleges and Universities in Henan Province (No. 19A310020 and 16A180015), Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine (No. XTCX-2015-ZD3) and Scientific and Technological Research Project of Henan Province (No. 182102311136). Declaration of Interests: The authors declare no competing financial interest. Ethics Approval Statement: All animal experiments were approved by the Ethics Committee of Xinxiang Medical University.