Osteoarthritis (OA) is a common chronic joint disease, the etiology of which is complex. Disturbance to proinflammatory and anti-inflammatory signaling pathways is a major cause of OA. MicroRNAs (miRNAs/miR) are a group of endogenous, short, non-coding RNAs, the expression profile of which is disturbed in the cartilage of patients with OA. To determine the function of miRNAs during the progression of OA, the present study detected the expression levels of nine candidate miRNAs in cartilage samples from 33 patients with OA. The results demonstrated that miR-26a, miR-26b, miR-138 and miR-140 were downregulated in patients with OA. As predicted by a bioinformatics analysis and confirmed by luciferase assay and western blotting, the present study revealed that miR-26a and miR-26b are able to suppress karyopherin subunit alpha 3 (KPNA3) expression by targeting its 3′-untranslated region. Since KPNA3 is an important mediator that modulates nuclear factor (NF)-κB p65 translocation, the present study examined the impact of miR-26a and miR-26b on NF-κB signaling. The results indicated that transfection of cells with a miR-26a or miR-26b inhibitor may promote NF-κB p65 translocation from the cytoplasm to the nucleus via the upregulation of KPNA3. Furthermore, the expression levels of matrix metalloproteinase-3, −9, −13 and cyclooxygenase-2 were upregulated following transfection with a miR-26a or miR-26b inhibitor. These results indicate that downregulation of miR-26a and miR-26b may contribute to the pathogenesis of OA via promotion of the NF-κB signaling pathway. The present study sheds light on the pathogenesis of OA and may provide a target for the development of therapeutic methods for the treatment of OA.
The present study aims to investigate the effects of miR-146a on the proliferation and apoptosis of human osteoarthritis (OA) chondrocytes by targeting tumour necrosis factor receptor-associated factor 6 (TRAF6) through nuclear factor-κB (NF-κB) signalling pathway. Human normal and OA chondrocytes were selected and divided into the normal group, blank group, negative control (NC) group, miR-146a mimics group, miR-146a inhibitors, miR-146a inhibitor + si-TRAF6 group and si-TRAF6 group. Quantitative real-time PCR (qRT-PCR) was applied to detect the expressions of miR-146a, TRAF6 mRNA and NF-κB mRNA. Western blotting was used to detect the protein expressions of TRAF6 and NF-κB. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis. Compared with normal chondrocytes, the expression of miR-146a decreased, while the mRNA and protein expressions of TRAF6 and NF-κB increased in OA chondrocytes. OA chondrocytes had a lower proliferation rate and a higher apoptosis rate than the normal chondrocytes. Compared with the blank, NC and si-TRAF6 groups, the expression of miR-146a increased in the miR-146a mimics group, but decreased in the miR-146a inhibitors and miR-146a inhibitor + si-TRAF6 groups. Compared with the blank, NC and miR-146a inhibitor + si-TRAF6 groups, the mRNA and protein expressions of TRAF6 and NF-κB decreased, cell proliferation rate increased and cell apoptosis rate decreased in the miR-146a mimics and si-TRAF6 groups, while opposite trends were observed in the miR-146a inhibitors group. Our study suggests that miR-146a could promote proliferation and inhibit apoptosis of OA chondrocytes by inhibiting TRAF6 expression and suppressing the activation of NF-κB signalling pathway.
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