MicroRNA‐34a‐5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2‐induced autophagy

Abstract

AbstractOsteoarthritis (OA), a late‐stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH‐OA and its upstream regulators remain obscure. Here, we first identified that the expression of SESN2 significantly decreased in the cartilage of DDH‐OA samples, with an expression trend negatively correlated with OA severity. Using RNA sequencing, we identified that the upregulation of miR‐34a‐5p may be an important factor for the decrease in SESN2 expression. Further exploring the regulation mechanism of miR‐34a‐5p/SESN2 is of great significance for understanding the mechanism of DDH occurrence and development. Mechanistically, we showed that miR‐34a‐5p could significantly inhibit the expression of SESN2, thereby promoting the activity of the mTOR signaling pathway. We also found that miR‐34a‐5p significantly inhibited SESN2‐induced autophagy, thereby suppressing the proliferation and migration of chondrocytes. We further validated that knocking down miR‐34a‐5p in vivo resulted in a significant increase in SESN2 expression and autophagy activity in DDH‐OA cartilage. Our study suggests that miR‐34a‐5p is a negative regulator of DDH‐OA, and may provide a new target for the prevention of DDH‐OA.