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  • Title: MicroRNA-146a-5p alleviates the pathogenesis of osteoarthritis by inhibiting SDF-1/CXCR4-induced chondrocyte autophagy.
    Author: Yang T, Li C, Li Y, Cai G, Wang G, He L, He C.
    Journal: Int Immunopharmacol; 2023 Apr; 117():109938. PubMed ID: 36863142.
    Abstract:
    BACKGROUND: SDF-1/CXCR4 signaling promotes osteoarthritis (OA) development. CXCR4 is a potential target of miR-146a-5p. This study investigated the therapeutic role and the underlying mechanism of miR-146a-5p in OA. METHODS: Human primary chondrocytes C28/I2 were stimulated with SDF-1. Cell viability and LDH release were examined. Chondrocyte autophagy was assessed using Western blot analysis, ptfLC3 transfection, and transmission electron microscopy. MiR-146a-5p mimics were transfected into C28/I2 cells to investigate the role of miR-146a-5p in SDF-1/CXCR4-induced autophagy of chondrocytes. An SDF-1-induced rabbit OA model was established to investigate the therapeutic role of miR-146a-5p in OA. Histological staining was performed to observe the morphology of osteochondral tissue. RESULTS: SDF-1/CXCR4 signaling promoted autophagy in C28/I2 cells, as demonstrated by increased LC3-II protein expression and autophagic flux induced by SDF-1. SDF-1 treatment significantly inhibited cell proliferation while promoting necrosis and autophagosome formation in C28/I2 cells. In the presence of SDF-1, miR-146a-5p overexpression in C28/I2 cells suppressed CXCR4 mRNA expression, LC3-II and Beclin-1 protein expression, LDH release, and autophagic flux. In addition, SDF-1 increased the autophagy of chondrocytes in rabbits and promoted the development of OA. Compared with the negative control, miR-146a-5p significantly reduced the morphological abnormalities of the rabbit cartilage that were induced by SDF-1, as well as the number of LC3-II-positive cells, protein expression of LC3-II and Beclin 1, and mRNA expression of CXCR4 in osteochondral tissue. These effects were reversed by the autophagy agonist rapamycin. CONCLUSIONS: SDF-1/CXCR4 promotes OA development by enhancing chondrocyte autophagy. MicroRNA-146a-5p may alleviate OA by suppressing CXCR4 mRNA expression and SDF-1/CXCR4-induced chondrocyte autophagy.
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