Sp7/Osterix is involved in the up-regulation of the mouse pro-α1(V) collagen gene (Col5a1) in osteoblastic cells

Sp7/Osterix, a transcription factor whose expression is restricted in osteoblasts, belongs to the Sp family of transcription factor that bind to G/C-rich sequences. Previous studies have identified a Sp1binding site in the proximal promoter region of the mouse Col5a1 gene, but it did not activate or...

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Bibliographic Details
Published in:Matrix biology 2010-10, Vol.29 (8), p.701-706
Main Authors: Wu, Yun-Feng, Matsuo, Noritaka, Sumiyoshi, Hideaki, Yoshioka, Hidekatsu
Format: Article
Language:English
Subjects:
Animals
Binding Sites - genetics
Bone formation
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Line
Collagen Type V - genetics
Gene Expression - drug effects
Gene Expression - genetics
Gene Expression Regulation - physiology
Gene regulation
Genes, Reporter - genetics
Glycerophosphates - pharmacology
Mice
Osteoblastic cell
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - metabolism
Promoter Regions, Genetic - genetics
Protein Binding - genetics
RNA, Small Interfering - genetics
Sp1 Transcription Factor - genetics
Sp1 Transcription Factor - metabolism
Sp7 Transcription Factor
Sp7/Osterix
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
Type V collagen
Up-Regulation - genetics
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Summary:Sp7/Osterix, a transcription factor whose expression is restricted in osteoblasts, belongs to the Sp family of transcription factor that bind to G/C-rich sequences. Previous studies have identified a Sp1binding site in the proximal promoter region of the mouse Col5a1 gene, but it did not activate or repress this gene in a mouse fibroblast cell line and a human rhabdomyosarcoma cell line. The purpose of the present study was to clarify the involvement of Sp7/Osterix in the mouse Col5a1 gene. A functional analysis revealed that mutation of the Sp1 binding site specifically decreased the promoter activity in osteoblastic cells. An overexpression of Sp7/Osterix significantly increased the promoter activity and the endogenous mRNA levels of the Col5a1 gene in osteoblastic cells. Conversely, siRNA-mediated knockdown of Sp7/Osterix decreased the promoter activity and the endogenous mRNA levels of the Col5a1 gene. These effects on promoter activity were canceled when the mutant construct of Sp1 binding site was introduced. Consistent with these data, the experiments using an osteoblast differentiation model showed increased promoter activity and endogenous mRNA levels, along with increased Sp7/Osterix during differentiation. Therefore, type V collagen appears to be involved in bone formation.
ISSN:0945-053X
1569-1802
DOI:10.1016/j.matbio.2010.09.002