Anti-chondrogenic role of nerve growth factor in osteoarthritis and human induced pluripotent stem cells-derived chondrogenesis model

Abstract

Abstract Background Nerve growth factor (NGF) is a neurotrophic factor involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Additionally, it has been suggested to play a role in osteoarthritis (OA). Previous studies have reported a relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the relationship between cartilage characteristics and NGF expression in the pathology of OA using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. Methods Synovial fluid was collected from patients (n = 3) with OA. NGF expression was confirmed in human OA cartilage tissue and synovial fluid. To confirm the role of NGF in chondrocalcinosis during OA development, hiPSCs-derived chondrogenic pellets were treated with NGF during differentiation. The expression of chondrogenic and hypertrophic (osteogenic) markers was confirmed using polymerase chain reaction and western blotting. Additionally, the expression of inflammatory cytokines and matrix metallopeptidase (MMP) was confirmed. Results NGF treatment decreased the expression of chondrogenic markers (SOX9, aggrecan, and collagen type II, alpha 1) in chondrogenic pellets, whereas the expression of hypertrophy markers (collagen type X, alpha 1 and vascular endothelial growth factor A) was increased. The expression of inflammatory cytokines and MMPs also increased in NGF-treated chondrogenic pellets. Conclusions These findings suggest that increased NGF levels may induce chondrocalcinosis and osteophyte formation during OA progression and may represent a potential target for OA treatment.