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Blockade of ASIC1a inhibits acid-induced rat articular chondrocyte senescence through regulation of autophagy

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Abstract

Acid-sensitive ion channel 1a (ASIC1a), which is abundant in chondrocytes, can sense changes in extracellular acidification. Our previous data demonstrated that ASIC1a is involved in acid-induced rat articular chondrocyte damage in osteoarthritis; however, its specific mechanisms remain unclear. The present study aims to explore the role of ASIC1a in rat articular chondrocyte senescence. RNA-seq transcriptome analysis identified senescence-associated secretory phenotype and matrix metalloproteinases genes were overexpressed by extracellular acidification (pH 6.0) in rat articular chondrocytes. An increase in senescence-associated β-galactosidase and senescence-related markers p16, p21 and p53 was observed in the pH 6.0-treated group compared with the control group. Acid-induced senescence-related markers could be blocked by the ASIC1a-specific inhibitor psalmotoxin-1 in rat articular chondrocytes and human immortalized C28/I2 chondrocyte cell lines. Moreover, our results showed that extracellular acidification increased autophagosomes and the autophagy-related proteins LC3B-II and Beclin-1; these effects could also be reversed by psalmotoxin-1 treatment, indicating ASIC1a participated in acid-induced chondrocyte autophagy. Blocking ASIC1a-mediated autophagy with chloroquine also inhibited senescence-related markers, decreased ROS expression, and restored cell membrane potential induced by pH 6.0 treatment. Taken together, these findings suggested that ASIC1a may be involved in acid-induced rat articular chondrocyte senescence by activating autophagy, which provides a potential therapeutic strategy for the treatment of osteoarthritis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 82071591, 81902182) and the Natural Science Foundation of Anhui Province (Grant No. 1908085QH317).

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  1. Yang Yang, Jie Ding and Yong Chen contributed equally.

Authors and Affiliations

  1. Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China

    Yang Yang, Jie Ding, Yong Chen, Ganggang Ma, Xin Wei, Renpeng Zhou & Wei Hu

  2. The Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China

    Renpeng Zhou & Wei Hu

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Yang, Y., Ding, J., Chen, Y. et al. Blockade of ASIC1a inhibits acid-induced rat articular chondrocyte senescence through regulation of autophagy. Human Cell 35, 665–677 (2022). https://doi.org/10.1007/s13577-022-00676-7

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