| First Author | Sato MM | Year | 2009 |
| Journal | Genes Cells | Volume | 14 |
| Issue | 2 | Pages | 141-53 |
| PubMed ID | 19170762 | Mgi Jnum | J:146869 |
| Mgi Id | MGI:3838697 | Doi | 10.1111/j.1365-2443.2008.01258.x |
| Citation | Sato MM, et al. (2009) Bone morphogenetic protein-2 enhances Wnt/beta-catenin signaling-induced osteoprotegerin expression. Genes Cells 14(2):141-53 |
| abstractText | Wnt/beta-catenin signaling plays an important role in the developing skeletal system. Our previous studies demonstrated that Wnt/beta-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/beta-catenin and BMP-2 in regulating the expression of osteoprotegerin (OPG) and of the receptor activator of NFkappaB ligand (RANKL). OPG expression was induced by Wnt/beta-catenin signaling in C2C12 cells and osteoblastic MC3T3-E1 cells. Silencing of glycogen synthase kinase-3beta also increased OPG expression. In contrast, R expression was suppressed by Wnt/beta-catenin signaling. In a transfection assay, beta-catenin induced the activity of a reporter gene, a 1.5 kb fragment of the 5'-flanking region of the OPG gene. Deletion and mutation analysis revealed that Wnt/beta-catenin signaling regulates transcription of OPG via a promoter region containing two Wnt/beta-catenin responsive sites. BMP-2 enhanced Wnt/beta-catenin-dependent transcriptional activation of the OPG promoter. In response to BMP-2 stimulation, Smad 1 and 4 interacted with Wnt/beta-catenin responsive sites. These results show that the regulation of OPG expression is mediated through two transcription pathways that involve the OPG promoter. |
