title: OASIS modulates hypoxia pathway activity to regulate bone angiogenesis.
abstract: OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1α (HIF-1α) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis(-/-)) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1α through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis(-/-) osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis(-/-) mice. These results suggest that OASIS affects the expression of HIF-1α target genes through the protein interaction with HIF-1α, and that OASIS-HIF-1α complexes may play essential roles in angiogenesis during bone development.
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Asada
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuhisa
authors.affiliation: Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.affiliation: Department of Molecular Biology and Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshimoto
authors.affiliation: Department of Molecular Biology and Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.affiliation: Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000098:blood supply* / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020218:Response Elements; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009419:Nerve Tissue Proteins