NGF contribute to acid-induced articular chondrocytes apoptosis by modulating ASIC1a/NLRP1/Caspase-1 signaling axis

• 1、Department of Pharmacy, The Second Hospital of AnHui Medical University

Abstract：Objective: Nerve growth factor (NGF) is key regulators in the pathogenesis of the rheumatoid arthritis (RA) diseases. However, the potential role of NGF in RA remains unclear. It has been shown that ASIC1a is an extracellular pH sensor in articular chondrocytes and RA. Moreover, NGF modulates the expression of ASICs in sensory neurons sensitization. In this study, we examined whether NGF contribute to ASIC1a expression could affect acid-induced apoptotic injury to articular chondrocytes. Methods: The primary rat articular chondrocytes were isolated from Sprague-Dawley rats. Apoptosis of chondrocytes was observed by the terminal deoxyribonucleotidyl transferase- mediated dUTP nick-end labeling method as well as propidium iodide labeling methods. Treatment of articular chondrocytes with NGF, ASIC1a-siRNA and acid, the expression levels of NGF, ASIC1a, NLRP1 and Caspase-1 were examined by qRT-PCR and western blotting, respectively. Results: We found that up-regulation of ASIC1a in acid-induced articular chondrocytes is associated with NGF treatment. Knockdown of ASIC1a inhibited NLRP-1 expression in acid-induced articular chondrocytes. Knockdown of ASIC1a suppressed acid-induced articular chondrocytes apoptosis. Moreover, we investigated the effect of ASIC1a on NLRP1/Caspase-1 pathway. Our results demonstrated that NGF contribute to acid-induced articular chondrocytes apoptosis by modulating ASIC1a/NLRP1/Caspase-1 signaling axis. Conclusion: Taken together, these results indicated that NGF promotes acid-induced articular chondrocytes apoptosis by up-regulation of ASIC1a/NLRP1/Caspase-1 signaling axis.

keywords： Nerve growth factor ASIC1a Articular chondrocytes Apoptosis

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