title: OBIF, an osteoblast induction factor, plays an essential role in bone formation in association with osteoblastogenesis.
abstract: In vertebrate bone formation, the functional mechanisms of transcription factors in osteoblastic differentiation have been relatively well elucidated; however, the exact roles of cell-extrinsic molecules are less clear. We previously identified human and mouse Obif, an osteoblast induction factor, also known as Tmem119, which encodes a single transmembrane protein. OBIF is predominantly expressed in osteoblasts in mouse. While exogenous Obif expression stimulated osteoblastic differentiation, knockdown of Obif inhibits the osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells. In order to investigate an in vivo role of OBIF in bone formation, we generated Obif-deficient mice by targeted gene disruption. Analyses of micro-computed tomography (mCT) revealed that Obif(-/-) mice exhibit significantly reduced cortical thickness in the mid-shaft of the femur at postnatal day 14 (P14). Furthermore, progressive bone hypoplasia is observed after 8 weeks. The expression levels of osteoblast marker genes, Collagen 1a1, Osteopontin, Runx2, and Osterix, in the calvaria were decreased in Obif(-/-) mice at P4. These data indicate that Obif plays an essential role in bone formation through regulating osteoblastogenesis.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565-0874, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuhashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamoto
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Moriishi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Muranishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.forename: Koji
authors.initials: K
authors.lastname: Terada
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005269:Femur / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005819:Genetic Markers; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000196:embryology; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D005819:Genetic Markers; D008565:Membrane Proteins; C547179:Obif protein, mouse; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C506896:Spp1 protein, mouse; D014157:Transcription Factors; D053495:Osteopontin