LAUSR

Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia‐reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA‐23b (miR‐23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR‐23b, MDM4, and the p53 signaling pathway‐related genes was characterized in cartilaginous tissues. Then, miR‐23b mimics or inhibitors were applied for the elevation or the depletion of the miR‐23b expression and siRNA‐MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real‐time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR‐23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR‐23b through. Downregulated miR‐23b increased the expression of MDM4, AKT, and Bcl‐2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR‐23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR‐23b was observed after MDM4 knocked down. Our results indicate that silencing miR‐23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.