title: MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb.
abstract: Osteoblastic differentiation is regulated by various factors, including hormones and transcription factors. Runt-related transcription factor 2 (Runx2) is an essential player in osteoblastogenesis and transactivates its molecular target by creating a protein complex with its hetero-dimeric partner core binding factor beta (Cbfb). However, the molecular regulation of Cbfb expression remains unknown. Here, we identified miR-145 as a crucial regulator of Cbfb expression. The expression of miR-145 increased during osteoblastogenesis, indicating that miR-145 works as an inhibitor of osteoblastogenesis. Stable expression of miR-145 decreased endogenous Cbfb expression and inhibited osteoblastogenesis, in cooperation with miR-34c. Furthermore, miR-145 decreased bone regeneration in vivo. Our results indicate that miR-145 physiologically regulates osteoblast differentiation and bone formation via Cbfb expression by forming a regulatory microRNA network.
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Sunamura
authors.affiliation: Department of Emergency & Critical Care Medicine, School of Medicine, Keio University, Shinanomachi 35, Shinjyuku-ku, Tokyo 160-8582, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Haiden
authors.affiliation: Section of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Keio University, Shinanomachi 35, Shinjyuku-ku, Tokyo 160-8582, Japan.
authors.forename: Waka
authors.initials: W
authors.lastname: Bando
authors.affiliation: Department of Orthopedic Surgery, 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.affiliation: Department of Orthopedic Surgery and Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okawa
authors.affiliation: Department of Orthopedic Surgery and Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan. Electronic address: shu-tky@umin.ac.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001861:Bone Regeneration; D002454:Cell Differentiation; D002460:Cell Line; D050658:Core Binding Factor beta Subunit / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000502:physiology*; D011401:Promoter Regions, Genetic
chemical_list: C493692:CBFB protein, human; C493693:Cbfb protein, mouse; D050658:Core Binding Factor beta Subunit; C541010:MIRN145 microRNA, human; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs
keywords: Core binding factor beta; MicroRNA; Osteoblast