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Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes

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Abstract

Rheumatoid arthritis (RA) is a degenerative joint disease that is caused by multiple pathogenic factors. However, the precise etiology of RA is still unknown. Our previous studies demonstrated that acid-sensing ion channel 1a (ASIC1a)-mediated articular chondrocyte apoptosis played a key role in the progression of RA. In this study, we aim to explore whether ASIC1a mediates autophagy or not and the effect of autophagy on ASIC1a-mediated apoptosis. Primary articular chondrocytes, extracted from rat knee joints, were exposed to different concentrations of concentrated hydrochloric acid for different time intervals in vitro. The results indicated that extracellular acid treatment induced autophagy of rat articular chondrocytes. Moreover, inhibition of ASIC1a with either psalmotoxin 1 or ASIC1a short hairpin RNA reduced the autophagy flux. The results suggested that ASIC1a mediated acid-induced autophagy. Pretreatment with autophagy antagonist 3-methyladenine decreased the autophagy, but increased the apoptosis mediated by ASIC1a. Furthermore, knockdown of Beclin 1 by small interfering RNA attenuated autophagy but potentiated ASIC1a-mediated apoptosis of rat articular chondrocytes. Taken together, these findings suggested that both inhibition and silencing of autophagy could enhance ASIC1a-mediated apoptosis in rat articular chondrocytes, and therefore, autophagy is likely to be a new mechanism involved in ASIC1a-mediated apoptosis of articular chondrocytes during the pathogenesis of RA.

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Acknowledgements

This work was supported by the National Science Foundation of China (Nos. 81271949, 30873080) and Anhui Provincial Natural Science Foundation (1408085MH151).

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Ya-Ya Xie, Yue Li, Ren-peng Zhou, Bei-Bei Dai, Yue-jiao Qian, Xiao-shan Wu, Jin-fang Ge & Fei-hu Chen

  2. Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, People’s Republic of China

    Wei Hu

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  1. Ya-Ya Xie
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Ya-Ya Xie and Yue Li participated equally and should share “first authorship”.

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Xie, YY., Li, Y., Zhou, Rp. et al. Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes. Mol Cell Biochem 443, 181–191 (2018). https://doi.org/10.1007/s11010-017-3223-6

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  • DOI: https://doi.org/10.1007/s11010-017-3223-6

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