Nitric oxide-caused rabbit chondrocyte apoptosis is linked to cytoskeletal protein proteolysis anomaly through intracellular JNK and ERK signal pathways

Backgrounds Nitric oxide (NO) plays a key role in the pathological chondrocyte apoptosis of osteoarthritis (OA). Cytoskeletal proteins form cytoskeleton network to maintain normal chondrocyte structure and function. JNK and ERK pathways are the signal pathways involved in the cell apoptosis. The role of cytoskeletal proteins in cytoskeleton perturbation and cell apoptosis was investigated in this study. Objectives In vitro cell apoptosis was induced in rabbit articular chondrocytes by NO donor Sodium Nitroprusside (SNP). The JNK-specific inhibitor SP600125 and ERK-specific inhibitor PD98059 were employed to clarify the mechanism. The level of apoptosis was evaluated by TUNEL assay and Annexin V flow cytometry. Results SNP induced concentration-dependent apoptosis, which was further enhanced by PD98059 but reduced by SP600125. Furthermore, PD98059 significantly increased caspase-3 expression and activity respectively, whereas SP600125 reduced caspase-3 expression and activity. SP600125 increased the cytoskeletal protein mRNA and protein expression, while PD98059 decreased them. Conclusion Intracellular JNK/ERK pathways were involved in chondrocyte apoptosis induced by SNP through oppositely regulated effects on cytoskeletal proteins; ERK pathway protected cytoskeletal protein from dissolution via inhibition of caspase-3 activation, while JNK pathway promoted the dissolution via activation of caspase-3 activity.