Long non-coding RNA DANCR regulates the proliferation and osteogenic differentiation of human bone-derived marrow mesenchymal stem cells via the p38 MAPK pathway

摘要

Long non-coding RNAs (lncRNAs) have been established to participate in the complex network of various biological processes and play important roles in the differentiation of mesenchymal stem cells (MSCs). However, the roles of lncRNAs in the mechanisms of the osteogenic differentiation of human bone marrow-derived MSCs (HBMSCs) are poorly understood. Thus, this study aimed to investigate the effects of the lncRNA, differentiation antagonizing non-protein coding RNA (DANCR), on the proliferation and osteogenic differentiation of HBMSCs. We found that lncRNA DANCR was abnormally decreased in HBMSCs during osteogenic differentiation. DANCR knockdown induced by transfection with siRNA targeting DANCR (si-DANCR) significantly enhanced the proliferation and osteogenic differentiation of HBMSCs. By contrast, when DANCR expression was enhanced by transfection with a DANCR overexpression vector (pcDNA-DANCR), the proliferation and osteogenic differentiation of the HBMSCs were markedly inhibited. We further found that mitogen-activated protein kinase (MAPK) pathways were involved in the DANCR-mediated proliferation and osteogenic differentiation of HBMSCs. Moreover, DANCR was found to mediate the proliferation and osteogenic differentiation of HBMSCs via p38 MAPK inactivation, but not via extracellular signal-regulated protein kinase (ERK)1/2 or c-Jun N-terminal kinase (JNK) MAPKs, but. Combination treatment (pcDNA-DANCR and with the p38 specific inhibitor, SB203580) led to synergistic inhibitory effects, and these inhibitory effects were reversed by DANCR knockdown. These findings not only provide a novel interpretation for the mechanisms of the proliferation and osteogenic differentiation of HBMSCs, but also suggest that DANCR may be a novel therapeutic target for bone-destructive diseases in the future.