Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes.
Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes.
复制标题
自噬对酸敏感离子通道 1a 介导的大鼠关节软骨细胞凋亡的影响。
DOI：
10.1007/s11010-017-3223-6
复制
发表时间：
2017
影响因子：
4.3
通讯作者：
Chen Fei-Hu
中科院分区：
文献类型：
--
作者：
Xie Ya-Ya;Li Yue;Zhou Ren-Peng;Dai Bei-Bei;Qian Yue-Jiao;Wu Xiao-Shan;Ge Jin-Fang;Hu Wei;Chen Fei-Hu
类风湿性关节炎（RA）是一种由多种致病因素引起的退行性关节疾病。然而，RA 的确切病因仍不清楚。我们之前的研究表明，酸敏感离子通道1a（ASIC1a）介导的关节软骨细胞凋亡在RA的进展中发挥着关键作用。本研究旨在探讨ASIC1a是否介导自噬以及自噬对ASIC1a介导的细胞凋亡的影响。从大鼠膝关节中提取的原代关节软骨细胞在体外暴露于不同浓度的浓盐酸中不同的时间间隔。结果表明，细胞外酸处理诱导大鼠关节软骨细胞自噬。此外，用 psalmotoxin 1 或 ASIC1a 短发夹 RNA 抑制 ASIC1a 会减少自噬通量。结果表明 ASIC1a 介导酸诱导的自噬。用自噬拮抗剂 3-甲基腺嘌呤预处理可降低自噬，但增加 ASIC1a 介导的细胞凋亡。此外，通过小干扰 RNA 敲低 Beclin 1 可减弱自噬，但会增强 ASIC1a 介导的大鼠关节软骨细胞凋亡。综上所述，这些研究结果表明，自噬的抑制和沉默均可以增强大鼠关节软骨细胞中ASIC1a介导的细胞凋亡，因此，自噬可能是RA发病过程中参与ASIC1a介导的关节软骨细胞凋亡的新机制。
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.