title: Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.
abstract: Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a member of the CREB/ATF family and has a transmembrane domain. OASIS is processed by regulated intramembrane proteolysis (RIP) in response to ER stress, and is highly expressed in osteoblasts. OASIS(-/-) mice exhibited severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts, which showed abnormally expanded rough ER, containing of a large amount of bone matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1 through an unfolded protein response element (UPRE)-like sequence in the osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of which is required for bone formation. Additionally, RIP of OASIS is accelerated by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hino
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiya
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsumagari
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saitoh
authors.forename: Riko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Furuichi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger