Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China.
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei, China.
J Cell Mol Med. 2019 Nov;23(11):7879-7884. doi: 10.1111/jcmm.14629. Epub 2019 Sep 11.
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.
类风湿关节炎（RA）是一种慢性、系统性自身免疫性疾病，最终会导致关节畸形和功能丧失。先前的研究表明，自噬与 RA 的发展密切相关。尽管自噬和细胞凋亡是两种不同形式的程序性细胞死亡，但它们之间的关系与 RA 仍不清楚。在这项研究中，我们探讨了自噬对体内和体外关节软骨细胞凋亡的影响。佐剂关节炎（AA）和酸诱导的原代关节软骨细胞凋亡分别作为体内和体外模型。在 AA 大鼠关节软骨的不同阶段（15 天、25 天和 35 天），动态观察到关节软骨细胞的自噬和凋亡。此外，自噬抑制剂 3-甲基腺嘌呤（3-MA）增加了 AA 大鼠的软骨细胞凋亡和关节软骨损伤，而自噬激活剂雷帕霉素则降低了 AA 大鼠的软骨细胞凋亡。此外，3-MA 的预处理增加了酸诱导的软骨细胞凋亡，而雷帕霉素的预处理减少了体外酸诱导的软骨细胞凋亡。这些结果表明，自噬可能是治疗 RA 的一个潜在靶点。
