title: miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity.
abstract: Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation.
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: 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.|Department of orthopedics, No.454 Hospital of PLA, Nanjing, Jiangsu 210002, P.R. 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: 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.
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: 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: D000818:Animals; D001862:Bone Resorption / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D004195:Disease Models, Animal; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D014893:Weightlessness
chemical_list: C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat