Downregulated microRNA‐106 inhibits apoptosis and promotes proliferation and differentiation of chondrocytes in osteoarthritis through restraining the activation of Wnt/β‐catenin pathway

Abstract

AbstractOsteoarthritis (OA) is a degenerative disease with poor prognosis. Recent studies demonstrated the change of several microRNAs (miRNAs) in OA and their possibility to be regarded as diagnostic markers for OA. This study was to investigate how miR‐106 mediated the Wnt3a/β‐catenin signaling pathway in the regulation of proliferation, differentiation, and apoptosis of chondrocytes in OA mice. A mouse OA model was established by using a modified Hulth modeling method. The mice were injected with miR‐106 Agomir or Antagomir to elucidate the role of miR‐106 in pathological structure, cell apoptosis, and inflammation reaction in cartilage tissues of OA mice. The chondrocytes were introduced with miR‐106 Inhibitor or Mimic to probe into the role of miR‐106 in proliferation, differentiation, and apoptosis of chondrocytes. RT‐qPCR and Western blot analysis tested miR‐106, Wnt3a, and β‐catenin expression. Elevated miR‐106 and activated Wnt3a/β‐catenin pathway were presented in cartilage tissues of OA mice. Inhibited miR‐106 declined Wnt3a and β‐catenin expression in cartilage tissues of mice of OA. Declined miR‐106 alleviated pathological changes, inhibited cell apoptosis and inflammation in cartilage tissues, promoted proliferation and differentiation, and suppressed apoptosis of chondrocytes in OA mice. Inactivating the Wnt3a/β‐catenin signaling pathway reversed the up‐regulated miR‐106‐induced suppression of chondrocyte proliferation and deterioration of bone and joint injury. This work makes it clear that downregulated miR‐106 suppresses apoptosis, and promotes the proliferation and differentiation of OA chondrocytes via inactivation of the Wnt3a/β‐catenin pathway, offering a novel treatment approach for human OA.