miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

The present study aimed to investigate the effect and underlying mechanism of microRNA (miR)-4262 in the development of osteoarthritis (OA) in rats. Primary chondrocytes were separated from Sprague-Dawley rats and then treated with tumor necrosis factor-alpha (TNF-alpha). The level of miR-4262 was detected in TNF-alpha-treated chondrocytes, and then the miR-4262 or its target gene sirtuin type 1 (SIRT1) level was overexpressed, or knocked down. Furthermore, cell viability, cell apoptosis, cell autophagy and matrix synthesis, as well as the expressions of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were detected. miR-4262 was significantly overexpressed in TNF-alpha-treated chondrocytes compared with untreated cells (P< 0.05). TNF-alpha treatment or miR-4262 overexpression significantly decreased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as increased the apoptotic rate in chondrocytes (P< 0.05). Overexpression of SIRT1 significantly increased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as decreased the apoptotic rate in TNF-alpha-treated chondrocytes (P< 0.05). In addition, the effects of miR-4262 on cell viability, cell apoptosis, cell autophagy and matrix synthesis were inhibited by SIRT1 (P< 0.05). Furthermore, upregulated miR-4262 remarkably increased the expressions of phosphorylated (p)-PI3K, p-AKT and p-mTOR (P< 0.05) in TNF-alpha treated chondrocytes. The present study revealed that the upregulation of miR-4262 may promote the occurrence and development of OA in rats by regulating cell viability, cell apoptosis, cell autophagy, and matrix synthesis. Furthermore, these roles of miR-4262 may be associated with PI3K/AKT/mTOR signaling pathway.