miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

摘要

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated β-galactosidase (SA-βGal), p16 , p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1β (IL-1β)-induced OA chondrocytes that pretransfection with miR-140 effectively inhibited the expression of SA-βGal, p16 , p21, p53, and γH2AX. Furthermore, results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.