Aquaporin-4 Blockage by siRNA Protects Rat Articular Chondrocytes from IL-1 beta-induced Apoptosis by Inhibiting p38 MAPK Signal Pathway

作者：Cai, Li; Lei, Chao; Li, Rong^*; Chen, Wei-na; Li, Chun-mei

来源：Annals of Clinical and Laboratory Science, 2017, 47(5): 563-571.

• apoptosis
• aquaporin-4
• articular chondrocyte
• interleukin-1 beta
• p38 MAPK
• rheumatoid arthritis

Accumulating evidence reveals that articular chondrocytes undergo increased apoptosis in rheumatoid arthritis (RA) and inhibiting chondrocyte apoptosis might be a promising therapeutic strategy. We recently found that aquaporin-4 (AQP4) protein level in the cartilage of rats with adjuvant-induced arthritis was higher than normal rats. Herein, cultured rat articular chondrocyte impaired by interleukin-1 beta (IL-1 beta) was used as an in vitro model of chondrocyte apoptosis. We observed the protective effect of AQP4 blockage by siRNA on IL-1 beta-induced chondrocyte apoptosis and explored the underlying mechanisms. Our findings revealed that AQP4 siRNA protected articular chondrocytes from IL-1 beta-induced apoptosis, evidenced by increased cell proliferation (MTT assay), few observations of apoptotic morphologic changes (Hoechst 33258 staining assay) and decreased cell apoptosis rates (Annexin V-FITC/PI staining assay). Additionally, AQP4 siRNA remarkably decreased Bax and caspase 3 mRNA levels and increased Bcl-2 mRNA level, accompanied by reducing phosphorylated-p38 (P-p38) protein level, without affecting p38 protein. The above effects of AQP4 siRNA were similar to SB203580, a specific p38 inhibitor. Together, AQP4 siRNA attenuated IL-1 beta-induced chondrocyte apoptosis by regulating apoptosis-related gene expressions and inhibiting p38 MAPK. Our results provide experimental evidence that AQP4 inhibition contributes to preventing chondrocyte apoptosis in joint diseases such as RA and provide a novel therapeutic target for RA.

• 出版日期2017-10
• 单位安徽医科大学