Interference of miR-212 and miR-384 promotes osteogenic differentiation via targeting RUNX2 in osteoporosis

The increasing level of osteogenic (OS) differentiation of bone marrow derived mesenchymal stem cells (MSCs) could be potentially used to relieve the signs and symptoms associated with osteoporosis (OP). Inhibition of osteoprotegerin (OPG)/Receptor Activator of Nuclear factor-Kappa B Ligand (RANKL) pathway plays an important role in OS differentiation, leading to excessive osteoclasts and reduction of osteoblasts, and finally causing OP. Recent studies revealed that microRNAs exert an essential role in regulating OS differentiation. Here, we investigated the dysregulation of miR-212 and miR-384 and the mechanism by which they are involved in OS differentiation-induced MSCs. Quantitative real-time PCR revealed that miR-212 and miR-384 were significantly upregulated in an OP animal model, but markedly downregulated in OS differentiation-induced MSCs. Interference of miR-212 and miR-384 promoted OS differentiation and alleviated OP by targeting RUNX2 in vitro and in vivo. Notably, the inhibition of miR-212 and miR-384 promoted OS differentiation via upregulating RUNX2, and activating OPG/RANKL pathway. Together, our findings demonstrated that interference of miR-212 and miR-384 alleviated OP via RUNX2/OPG/RANKL pathway, providing a novel target of treating OP.,Copyright © 2020 Elsevier Inc. All rights reserved.