title: A microRNA regulatory mechanism of osteoblast differentiation.
abstract: Growing evidence shows that microRNAs (miRNAs) regulate various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; however, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast differentiation remains elusive. Here, through comprehensive analysis of miRNAs expression during osteoblast differentiation, we show that miR-206, previously viewed as a muscle-specific miRNA, is a key regulator of this process. miR-206 was expressed in osteoblasts, and its expression decreased over the course of osteoblast differentiation. Overexpression of miR-206 in osteoblasts inhibited their differentiation, and conversely, knockdown of miR-206 expression promoted osteoblast differentiation. In silico analysis and molecular experiments revealed connexin 43 (Cx43), a major gap junction protein in osteoblasts, as a target of miR-206, and restoration of Cx43 expression in miR-206-expressing osteoblasts rescued them from the inhibitory effect of miR-206 on osteoblast differentiation. Finally, transgenic mice expressing miR-206 in osteoblasts developed a low bone mass phenotype due to impaired osteoblast differentiation. Our data show that miRNA is a regulator of osteoblast differentiation.
authors.affiliation: Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inose
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ochi
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimura
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Ren
authors.initials: R
authors.lastname: Xu
authors.forename: Shingo
authors.initials: S
authors.lastname: Sato
authors.forename: Makiko
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Satoko
authors.initials: S
authors.lastname: Sunamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Siomi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Arai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics
chemical_list: D018031:Connexin 43; D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse