Reduced miR-26a and miR-26b expression contributes to the pathogenesis of osteoarthritis via the promotion of p65 translocation

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.