Downregulation of miR-892b inhibits the progression of osteoarthritis via targeting cyclin D1 and cyclin D2

Abstract

BackgroundsOsteoarthritis (OA) is an orthopedic inflammatory disease which can cause functional disability and chronic pain. MiRNAs are known to play important roles in OA. To identify the targets for the treatment of OA, bioinformatics analysis was performed to explore differentially expressed miRNAs between OA and normal samples. MethodsBioinformatics analysis was conducted to identify differentially expressed miRNAs. To mimic OA in vitro, primary chondrocytes were stimulated with IL-1β. Meanwhile, flow cytometry was performed to detect the cell apoptosis and cycle distribution. In addition, protein and mRNA expressions were detected by Western blot and RT-qPCR, respectively. Finally, in vivo model of OA was constructed to investigate the function of miR-892b in OA. ResultsThe data indicated that miR-892b was identified to be upregulated in OA samples. Additionally, miR-892b antagomir markedly reversed IL-1β-induced growth decline of chondrocytes via inhibiting the apoptosis. IL-1β notably elevated the expressions of MMP1 and MMP13 and downregulated the level of Aggrecan in chondrocytes, while miR-892b antagomir reversed these phenomena. Meanwhile, cyclin D1 and cyclin D2 were the direct targets of miR-892b. In addition, IL-1β-induced G1 phase arrest in chondrocytes was partially abolished by of miR-892b antagomir. In vivo study indicated miR-892b antagomir could significantly alleviate the symptom of OA in a rat model. ConclusionMiR-892b antagomir inhibits the progression of OA via targeting Cyclin D1 and Cyclin D2. Thus, our finding might supply a novel target for OA treatment.