title: miR-21 synergizes with BMP9 in osteogenic differentiation by activating the BMP9/Smad signaling pathway in murine multilineage cells.
abstract: Bone morphogenetic proteins (BMPs), particularly BMP9, have been shown to promote the osteogenic differentiation of murine multilineage cells (MMCs) and to promote bone formation in bone diseases; however, the mechanisms involved remain poorly understood. MicroRNAs (miRNAs or miRs) have been proven to regulate mesenchymal stem cell (MSC) differentiation. In this study, we identified a novel mechanism that unravels the functional axis of a key miRNA (miR-21) which contributes to BMP9‑induced osteogenic differentiation. We screened differentially expressed miRNAs in MMCs during BMP9‑induced osteogenic differentiation and found that miR-21 was significantly upregulated by BMP9 during the osteogenesis of MMCs. Furthermore, miR-21 was confirmed to promote the osteogenic differentiation of the MMCs by suppressing Smad7, which negatively regulates the osteogenic differentiation of MMCs. The upregulation of miR-21 may promote the osteogenic differentiation of MMCs in synergy with BMP9. The findings of our study revealed a novel function of miR-21, and suggest that the overexpression of miR-21 contributes to bone formation by promoting BMP9‑induced osteogenic differentiation. Our data may provide a molecular basis for the development of novel therapeutic strategies to treat bone diseases, such as osteoporosis and other inflammatory bone diseases.
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiling
authors.initials: Q
authors.lastname: Song
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zuchuan
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D055427:Growth Differentiation Factor 2 / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002118:Calcium