open access

https://hdl.handle.net/2115/38890

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

Wnt/β-catenin signaling and osteoprotegerin

英語

osteoblasts

2009-02

Blackwell

Genes to Cells

14(2)

141-153

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.

学術雑誌論文

Accepted Manuscript

The definitive version is available at www.blackwell-synergy.com

1356-9597

1365-2443

AA11078945