Therapeutic effect of Resveratrol in the treatment of osteoarthritis via the MALAT1/miR-9/NF-κB signaling pathway

The aim of the current study was to explore the role of Resveratrol (Res) in osteoarthritis (OA) and its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the relative expression levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), microRNA-9 (miR-9), nuclear factor kappa B subunit 1 (NF-kappa B1), interleukin (IL)-6, matrix metallopeptidase 13 (MMP-13) and caspase-3 in vitro and in the in vivo model of OA, as well as examining the effect of Res on MALAT1, miR-9 and NF-kappa B1, IL-6, MMP-13 and caspase-3 expression levels. Immunohistochemical analysis was performed to examine NF-kappa B1 and MMP-13 protein levels in the in vivo model of OA. Dual-luciferase reporter assays were used to confirm the regulatory relationship between miR-9 and MALAT1 and NF-kappa B1, as well as examining the effect of Res on the transcriptional activation of MALAT1 promoter. Furthermore, the effect of Res on cell proliferation in vitro was examined by MTT assay. The relative mRNA expression levels of MALAT1 and NF-kappa B1 were significantly increased, while miR-9 expression was significantly decreased in the OA group compared with the sham group. Treatment with Res partially reversed the effects of OA on MALAT1, NF-kappa B1 and miR-9 expression. Similarly, the relative protein expression levels of NF-kappa B1, IL-6, MMP-13 and caspase-3 were significantly increased in the OA group compared with the sham group; however, treatment with Res partially reversed the effects of OA on the protein expression levels of NF-kappa B1, IL-6, MMP-13 and caspase-3. MALAT1 and NF-kappa B1 were identified as potential target genes of miR-9, and dual-luciferase assays were used to examine the effect of miR-9 on the luciferase activity of 3 ' UTR MALAT1 and NF-kappa B1. Treatment with Res suppressed the transcriptional activation of the MALAT1 promoter, thereby inhibiting MALAT1 expression. Additionally, the relative expression level of miR-9 significantly increased following treatment with Res in a dose-dependent manner, while the relative protein expression levels of NF-kappa B1, IL-6, MMP-13 and caspase-3 significantly decreased following treatment with Res compared with the control. Furthermore, treatment with Res significantly increased the growth rate of chondrocytes in a dose-dependent manner compared with the control. Taken together, these results suggest that direct targeting of the MALAT1/miR-9/NF-kappa B1/IL-6, MMP-13/caspase-3 axis may be a novel therapeutic strategy for the treatment of OA.