miR-138 suppressed the progression of osteoarthritis mainly through targeting p65

OBJECTIVE: MicroRNAs are reported to play key roles in regulating the main risk factors for osteoarthritis (OA) chondrogenesis. In the current study, we focused on miR-138, which has never been explored in OA.

PATIENTS AND METHODS: The expression of miR-138 and p65 was explored in the cartilage tissues of OA patients and compared with those of normal controls. We then explored the effects of miR-138 on NF-κB signaling activation in both human OA chondrocytes and chondrogenic SW1353 cells in the presence of 10 nM TNFα. The protein levels of p65, COX-2 and IL6 were determined using Western blot analysis. To validate the target gene of miR-138, a dual luciferase reporter assay was performed.

RESULTS: The level of miR-138 was markedly reduced in the OA cartilage tissues compared with those of normal controls. Real-time PCR analysis demonstrated that the level of miR-138 decreased after TNFα treatment for 3, 6, and 12 h in the normal chondrocytes and OA chondrocytes. Furthermore, overexpression of miR-138 suppressed the protein levels of p65, COX-2 and IL6 in human OA chondrocytes and chondrogenic SW1353 cells. A dual luciferase reporter assay demonstrated that miR-138 significantly suppressed the relative luciferase activity of pmirGLO-p65-3'UTR. More importantly, treatment with TNFα significantly enhanced the protein levels of p65, COX-2 and IL6. However, overexpression of miR-138 could partially abolish such effects.

CONCLUSIONS: We demonstrated that reduced miR-138 expression enhanced the destruction of the cartilage tissues among OA patients, mainly through targeting p65.

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