title: The IRE1α-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix.
abstract: During skeletal development, osteoblasts produce large amounts of extracellular matrix proteins and must therefore increase their secretory machinery to handle the deposition. The accumulation of unfolded protein in the endoplasmic reticulum induces an adoptive mechanism called the unfolded protein response (UPR). We show that one of the most crucial UPR mediators, inositol-requiring protein 1α (IRE1α), and its target transcription factor X-box binding protein 1 (XBP1), are essential for bone morphogenic protein 2-induced osteoblast differentiation. Furthermore, we identify Osterix (Osx, a transcription factor that is indispensible for bone formation) as a target gene of XBP1. The promoter region of the Osx gene encodes two potential binding motifs for XBP1, and we show that XBP1 binds to these regions. Thus, the IRE1α-XBP1 pathway is involved in osteoblast differentiation through promoting Osx transcription.
authors.affiliation: Department of Anti-aging Orthopedic Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Ghosh
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchikawa
authors.forename: Jiro
authors.initials: J
authors.lastname: Takito
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Takao
authors.initials: T
authors.lastname: Iwawaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; D008156:Luciferases; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases