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Bone morphogenetic protein-2 enhances Wnt/β-catenin signaling-induced osteoprotegerin expression

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Title: Bone morphogenetic protein-2 enhances Wnt/β-catenin signaling-induced osteoprotegerin expression
Other Titles: Wnt/β-catenin signaling and osteoprotegerin
Authors: Sato, Mari M. Browse this author
Nakashima, Aiko Browse this author
Nashimoto, Masayuki Browse this author
Yawaka, Yasutaka Browse this author
Tamura, Masato Browse this author →KAKEN DB
Keywords: osteoprotegerin
Wnt/β-catenin signaling
bone morphogenetic protein
Issue Date: Feb-2009
Publisher: Blackwell
Journal Title: Genes to Cells
Volume: 14
Issue: 2
Start Page: 141
End Page: 153
Publisher DOI: 10.1111/j.1365-2443.2008.01258.x
PMID: 19170762
Abstract: Wnt/β-catenin signaling plays an important role in the developing skeletal system. Our previous studies demonstrated that Wnt/β-catenin signaling inhibits the ability of bone morphogenetic protein (BMP)-2 to suppress myotube formation in the multipotent mesenchymal cell line C2C12 and that this inhibition is mediated by Id1. In this study, we examined the role of intracellular signaling by Wnt/β-catenin and BMP-2 in regulating the expression of osteoprotegerin (OPG) and of the receptor activator of NFkB ligand (RANKL). OPG expression was induced by Wnt/β-catenin signaling in C2C12 cells and osteoblastic MC3T3-E1 cells. Silencing of glycogen synthase kinase-3β also increased OPG expression. In contrast, RANKL expression was suppressed by Wnt/β-catenin signaling. In a transfection assay, β-catenin induced the activity of a reporter gene, a 1.5 kilobase fragment of the 5’-flanking region of the OPG gene. Deletion and mutation analyses revealed that Wnt/β-catenin signaling regulates transcription of OPG via a promoter region containing two Wnt/β-catenin responsive sites. BMP-2 enhanced Wnt/β-catenin-dependent transcriptional activation of the OPG promoter. In response to BMP-2 stimulation, Smad 1 and 4 interacted with these Wnt/β-catenin responsive sites. These results show that the regulation of OPG expression is mediated through two transcription pathways that involve the OPG promoter.
Rights: The definitive version is available at
Type: article (author version)
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 田村 正人

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