Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats
Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats
复制标题
自噬对佐剂性关节炎大鼠关节软骨细胞凋亡的影响
DOI：
10.1111/jcmm.14629
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Feihu Chen
中科院分区：
文献类型：
--
作者：
Ren-Peng Zhou;Fei Zhu;Xiao-Shan Wu;Sujing Song;Yong Chen;Chuanjun Zhu;Bei-Bei Dai;Xuewen Qian;Ke Wang;Wei Hu;Feihu Chen
风湿性关节炎（RA）是一种慢性全身性自身免疫性疾病，最终导致关节畸形和关节功能丧失。以往的研究表明自噬与类风湿关节炎的发生发展有密切关系。虽然自噬和凋亡是程序性死亡的两种不同形式，但它们与RA的关系尚不清楚。本研究探讨了自噬对关节软骨细胞凋亡的影响。分别采用佐剂性关节炎（AA）和酸诱导的原代关节软骨细胞凋亡作为体内和体外模型。动态观察AA大鼠关节软骨细胞自噬和凋亡的动态变化。自噬抑制剂3-甲基腺嘌呤（3-MA）可增加AA大鼠关节软骨细胞凋亡和关节软骨损伤，自噬激活剂雷帕霉素可减少软骨细胞凋亡和关节软骨损伤。此外，3-MA预处理增加了酸诱导的软骨细胞凋亡，而雷帕霉素预处理减少了酸诱导的软骨细胞凋亡。这些结果表明，自噬可能是一个潜在的治疗RA的目标。
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that eventually leads to joint deformities and loss of joint function. Previous studies have demonstrated a close relationship between autophagy and the development of RA. Although autophagy and apoptosis are two different forms of programmed death, the relationship between them in relation to RA remains unclear. In this study, we explored the effect of autophagy on apoptosis of articular chondrocytes in vivo and in vitro. Adjuvant arthritis (AA) and acid-induced primary articular chondrocyte apoptosis were used as in vivo and in vitro models, respectively. Articular chondrocyte autophagy and apoptosis were both observed dynamically in AA rat articular cartilage at different stages (15 days, 25 days and 35 days). Moreover, chondrocyte apoptosis and articular cartilage injury in AA rats were increased by the autophagy inhibitor 3-methyladenine (3-MA) and decreased by the autophagy activator rapamycin. In addition, pre-treatment with 3-MA increased acid-induced chondrocyte apoptosis, while pre-treatment with rapamycin reduced acid-induced chondrocyte apoptosis in vitro. These results suggest that autophagy might be a potential target for the treatment of RA.