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Bone morphogenetic protein-2 enhances Wnt/β-catenin signaling-induced osteoprotegerin expression
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 | osteoblasts |
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 www.blackwell-synergy.com |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/38890 |
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)
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Submitter: 田村 正人
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