title: miR-106b-5p and miR-17-5p suppress osteogenic differentiation by targeting Smad5 and inhibit bone formation.
abstract: Osteogenesis is a complex process which relies on the coordination of signals and transcription factors. BMP-2/Smad5 signal transduction pathway plays an important role in the process. Recent evidence indicates that microRNAs (miRNAs) act as important post-transcriptional regulators in a large number of biological processes including osteoblast differentiation. In this study, we investigated the effect of miR-106b-5p and miR-17-5p on osteogenic differentiation. We observed an obvious decreasement in miR-106b-5p and miR-17-5p levels during osteogenic differentiation. By using gain- and loss-of function experiments, we noticed that miR-106b-5p and miR-17-5p could suppress the osteogenic differentiation of C2C12 and MC3T3-E1 cells. In addition, we performed bioinformatic analysis, western blot and luciferase reporter assay to confirm that miR-106b-5p and miR-17-5p could regulate Smad5 expression negatively. When we inhibited Smad5 expression by siRNA, the effects of miR-106b-5p and miR-17-5p inhibition on osteogenesis of C2C12 cells could be significantly reversed by Smad5 RNA interference. Furthermore, silencing of miR-106b-5p and miR-17-5p in sham and ovariectomized (OVX) mice increased bone formation and bone mass, resulting in an improvement of trabecular microarchitecture. Taken together, these data showed that miR-106b-5p and miR-17-5p are novel Smad5 regulators, and they have a crucially physiological function in bone formation and osteoblast differentiation.
authors.affiliation: Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: qinfusj@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; C543614:Mirn17 microRNA, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse
keywords: Bone formation; Osteogenic differentiation; Smad5; miRNA