MicroRNA-590-5p targets transforming growth factor β1 to promote chondrocyte apoptosis and autophagy in response to mechanical pressure injury.

Abstract

This study aimed to investigate the role of miR-590-5p in chondrocyte apoptosis and autophagy in response to mechanical pressure injury in vitro, as well as to elucidate its regulatory mechanism in the pathogenesis of osteoarthritis. We applied mechanical pressure of 10 MPa to chondrocytes for 60 minutes to establish the chondrocyte model of experimentally induced mechanical injury. We then investigated the expression of miR-590-5p in the injury model and the effects of miR-590-5p dysregulation on the expression of cell apoptosis-related and autophagy-related proteins. Cell apoptosis was detected by flow cytometry. Moreover, the potential targets of miR-590-5p were investigated. Mechanical pressure injury resulted in a significantly increased expression of miR-590-5p. Suppression of miR-590-5p significantly increased chondrocytes viability, inhibited chondrocytes apoptosis and autophagy in response to mechanical pressure injury. In addition, mechanical pressure injury led to a decreased expression of transforming growth factor β1 (TGFβ1). Moreover, TGFβ1 was confirmed as a direct target of miR-590-5p. Knockdown of TGFβ1 significantly induced chondrocytes apoptosis and autophagy in response to mechanical pressure injury, which was contrary to the effects of miR-590-5p suppression. Furthermore, overexpression of TGFβ1 and miR-590-5p at the same time significantly reversed the effects of overexpression of miR-590-5p alone on chondrocytes apoptosis and autophagy. Our results indicate that upregulation of miR-590-5p may target TGFβ1 to promote chondrocyte apoptosis and autophagy in response to mechanical pressure injury, thus contributing to the pathogenesis of osteoarthritis.