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MicroRNA-21 promotes osteogenesis of bone marrow mesenchymal stem cells via the Smad7-Smad1/5/8-Runx2 pathway

Li, Xiaoyan, Guo, Lijia, Liu, Yitong, Su, Yingying, Xie, Yongmei, Du, Juan, Zhou, Jian, Ding, Gang, Wang, Hao, Bai, Yuxing, Liu, Yi
Biochemical and biophysical research communications 2017 v.493 pp. 928-933
Western blotting, alizarin, bone formation, bone marrow, mice, reverse transcriptase polymerase chain reaction, signal transduction, staining, stem cells
Bone marrow mesenchymal stem cells (BMMSCs) are pluripotent stem cells, and the osteogenic differentiation of BMMSCs has been drawing attention for a long time. Bone formation is regulated by numerous molecular and cellular signaling pathways, and the differentiation of BMMSCs is controlled by a well-defined genetic program. In the present study, we isolated BMMSCs from the bone cavities of wild-type (WT) and microRNA-21 knock-out (miR-21-KO) mice and found that miR-21 was significantly upregulated during the osteogenic differentiation of BMMSCs. Under osteoinductive conditions, ALP staining and alizarin red staining showed that the bone formation of BMMSCs from miR-21-KO mice was less than that of BMMSCs from WT mice. Consistently, RT-PCR and western blotting revealed that ALP and Runx2 expression levels in miR-21-KO mice were downregulated compared with those in WT mice. Meanwhile, the calvarial bone defects of miR-21-KO mice showed less newly formed bone than did those of WT mice. Additionally, the Smad7-Smad1/5/8-Runx2 axis showed the same tendency; Smad7 overexpression and the expression of phosphorylated Smad1/5/8 complex decreased when miR-21 was knocked down. We identified a novel mechanism by which microRNA-21 (miR-21) promotes the bone formation of BMMSCs and found that this process is regulated, in part, by the Smad7-Smad1/5/8-Runx2 pathway.