Mir-20a Regulates Osteogenesis Of Human Mesenchymal Stem Cells By Activating BMP Signaling

Human mesenchymal stem cells (hMSCs) are multipotent cells which can differentiate into different types of cells under the regulation of cell fate defining factors, such as osteoblast, adipocyte, chondrocyte and so on. As an osteoprogenitor,MSCs was very important to bone formation and regeneration. MicroRNAs (miRNA) are a class of short (20-24 nucleotied) non-coding RNA molecules that can bind to the 3'untranslated region of gene and regulate gene expression primarily through post-transcriptional repression or mRNA degradation. In recent ten years, researchers figured out that microRNAs (miRNAs) play important roles in a broad range of biological processes, including cell fate determination in embryonic stem cells, cell proliferation, differentiation and apoptosis. However, it is still elusive if miRNAs also define cell lineages in hMSCs.In this study, the capability of the family members of miR-17-92, especially miR-20a, in defining osteogenic lineage and regulating osteogenesis was investigated in hMSCs. Transfection of the ectopic expression of miR-20a was found to up-regulate the expression of Runx2 and BMPs in both transcriptional and translational levels. The up-regulation of Runx2 and BMPs, two critical defining factors of osteogenic lineage and the most important signaling molecules of osteogenic differentiation were noted as a result of the down-regulation of PPARγ. The miRNA also enhanced osteogenesis by suppressing BAMBI and CRIM1 expression, the antagonists of the BMP pathway. Our results demonstrate that miR-20a promotes osteogenesis of hMSCs. This is done by switching on osteogenic differentiation and activating BMP/Runx2 signaling via down-regulating the expression PPARγas well as inhibiting the expression of BAMBI and CRIM1.