Wnt/β-catenin signaling and osteoprotegerin
| Autor: | Mari Sato, Yasutaka Yawaka, Masato Tamura, Aiko Nakashima, Masayuki Nashimoto |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
musculoskeletal diseases Lymphoid Enhancer-Binding Factor 1 Bone Morphogenetic Protein 2 Smad Proteins SMAD Biology Bone morphogenetic protein Bone morphogenetic protein 2 Glycogen Synthase Kinase 3 Mice bone morphogenetic protein T Cell Transcription Factor 1 Genetics Animals RNA Messenger Promoter Regions Genetic GSK3B Cells Cultured beta Catenin Binding Sites Glycogen Synthase Kinase 3 beta Wnt signaling pathway osteoblasts LRP6 LRP5 Cell Biology Up-Regulation Wnt Proteins osteoprotegerin RANKL Gene Knockdown Techniques biology.protein Cancer research Protein Binding Signal Transduction Wnt/β-catenin signaling |
| Zdroj: | Genes to Cells. 14:141-153 |
| ISSN: | 1365-2443 1356-9597 |
| DOI: | 10.1111/j.1365-2443.2008.01258.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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