| First Author | Okamoto M | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 4493 | PubMed ID | 24670389 |
| Mgi Jnum | J:210471 | Mgi Id | MGI:5571231 |
| Doi | 10.1038/srep04493 | Citation | Okamoto M, et al. (2014) Noncanonical Wnt5a enhances Wnt/beta-catenin signaling during osteoblastogenesis. Sci Rep 4:4493 |
| abstractText | Wnt regulates bone formation through beta-catenin-dependent canonical and -independent noncanonical signaling pathways. However, the cooperation that exists between the two signaling pathways during osteoblastogenesis remains to be elucidated. Here, we showed that the lack of Wnt5a in osteoblast-lineage cells impaired Wnt/beta-catenin signaling due to the reduced expression of Lrp5 and Lrp6. Pretreatment of ST2 cells, a stromal cell line, with Wnt5a enhanced canonical Wnt ligand-induced Tcf/Lef transcription activity. Short hairpin RNA-mediated knockdown of Wnt5a, but not treatment with Dkk1, an antagonist of Wnt/beta-catenin signaling, reduced the expression of Lrp5 and Lrp6 in osteoblast-lineage cells under osteogenic culture conditions. Osteoblast-lineage cells from Wnt5a-deficient mice exhibited reduced Wnt/beta-catenin signaling, which impaired osteoblast differentiation and enhanced adipocyte differentiation. Adenovirus-mediated gene transfer of Lrp5 into Wnt5a-deficient osteoblast-lineage cells rescued their phenotypic features. Therefore, Wnt5a-induced noncanonical signaling cooperates with Wnt/beta-catenin signaling to achieve proper bone formation. |
