title: miR-33-5p, a novel mechano-sensitive microRNA promotes osteoblast differentiation by targeting Hmga2.
abstract: MicroRNAs (miRNAs) interfere with the translation of specific target mRNAs and are thought to thereby regulate many cellular processes. However, the role of miRNAs in osteoblast mechanotransduction remains to be defined. In this study, we investigated the ability of a miRNA to respond to different mechanical environments and regulate mechano-induced osteoblast differentiation. First, we demonstrated that miR-33-5p expressed by osteoblasts is sensitive to multiple mechanical environments, microgravity and fluid shear stress. We then confirmed the ability of miR-33-5p to promote osteoblast differentiation. Microgravity or fluid shear stress influences osteoblast differentiation partially via miR-33-5p. Through bioinformatics analysis and a luciferase assay, we subsequently confirmed that Hmga2 is a target gene of miR-33-5p that negatively regulates osteoblast differentiation. Moreover, miR-33-5p regulates osteoblast differentiation partially via Hmga2. In summary, our findings demonstrate that miR-33-5p is a novel mechano-sensitive miRNA that can promote osteoblast differentiation and participate in the regulation of differentiation induced by changes in the mechanical environment, suggesting this miRNA as a potential target for the treatment of pathological bone loss.
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.|Department of orthopedics, No. 454 Hospital of PLA, 210002, Nanjing, Jiangsu, China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Zebing
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Lianchang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hong
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Cao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D015870:Gene Expression; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology*; D034622:RNA Interference; D018474:Weightlessness Simulation
chemical_list: D020413:3' Untranslated Regions; D025743:HMGA2 Protein; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse