title: Sp7/Osterix induces the mouse pro-α2(I) collagen gene (Col1a2) expression via the proximal promoter in osteoblastic cells.
abstract: Bone is essentially composed of two components, hydroxyapatite and extracellular matrix proteins. The extracellular matrix of bone is primary composed of collagen, mostly type I collagen, with lesser amounts of other types of collagen such as type V collagen. Osteoblast differentiation is a multi-step process in which many classes of factors function in a coordinated manner. Sp7/Osterix, which binds to G/C-rich sequences, is a transcription factor that contributes to osteoblast differentiation. The present study aimed to clarify the involvement of Sp7/Osterix with the proximal promoter region of the mouse Col1a2 gene containing multiple G/C-rich sequences exist. Consequently, a functional analysis of the proximal mouse Col1a2 promoter showed that a substitution mutation of the second G/C-rich sequence from the transcription site specifically decreased the activity of osteoblastic cells. In addition, the experiments of overexpression of Sp7/Osterix and treatment with its specific siRNA showed that this G/C-rich sequence is responsible for the specific expression in osteoblastic cells. Consistent with these data, Sp7/Osterix bound to the region and increased the expression of the Col1a2 gene in association with osteoblast differentiation in the culture system.
authors.affiliation: Division of Radioisotope Research, Department of Research Support, Research Promotion Project, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan. Electronic address: yanoh@oita-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yano
authors.affiliation: Department of Cell Biology, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hamanaka
authors.affiliation: Department of Cell Biology, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura-Ota
authors.affiliation: Department of Matrix Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Matrix Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Matrix Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Matsuo
authors.affiliation: Department of Matrix Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D001482:Base Composition; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D034741:RNA, Small Interfering; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D008156:Luciferases
keywords: Bone formation; Gene expression; Osteoblastic cell; Sp7/Osterix; Type I collagen