title: miR-214 targets ATF4 to inhibit bone formation.
abstract: Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
authors.forename: Aiyuan
authors.initials: A
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Hou
authors.forename: Ke
authors.initials: K
authors.lastname: Lv
authors.forename: Guanghan
authors.initials: G
authors.lastname: Kan
authors.forename: Hongqing
authors.initials: H
authors.lastname: Cao
authors.forename: Heng
authors.initials: H
authors.lastname: Wu
authors.forename: Jinping
authors.initials: J
authors.lastname: Song
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Li
authors.forename: Mu
authors.initials: M
authors.lastname: Zhu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.forename: Songlin
authors.initials: S
authors.lastname: Peng
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Xie
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.forename: An
authors.initials: A
authors.lastname: Hong
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Bian
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Bai
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D000818:Animals; D016723:Bone Remodeling / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D019417:Hindlimb Suspension; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics
chemical_list: C081452:Atf4 protein, mouse; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D051701:Activating Transcription Factor 4