First Author | Tu X | Year | 2007 |
Journal | Dev Cell | Volume | 12 |
Issue | 1 | Pages | 113-27 |
PubMed ID | 17199045 | Mgi Jnum | J:117333 |
Mgi Id | MGI:3696006 | Doi | 10.1016/j.devcel.2006.11.003 |
Citation | Tu X, et al. (2007) Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell 12(1):113-27 |
abstractText | Wnt signaling regulates a variety of developmental processes in animals. Although the beta-catenin-dependent (canonical) pathway is known to control cell fate, a similar role for noncanonical Wnt signaling has not been established in mammals. Moreover, the intracellular cascades for noncanonical Wnt signaling remain to be elucidated. Here, we delineate a pathway in which Wnt3a signals through the Galpha(q/11) subunits of G proteins to activate phosphatidylinositol signaling and PKCdelta in the murine ST2 cells. Galpha(q/11)-PKCdelta signaling is required for Wnt3a-induced osteoblastogenesis in these cells, and PKCdelta homozygous mutant mice exhibit a deficit in embryonic bone formation. Furthermore, Wnt7b, expressed by osteogenic cells in vivo, induces osteoblast differentiation in vitro via the PKCdelta-mediated pathway; ablation of Wnt7b in skeletal progenitors results in less bone in the mouse embryo. Together, these results reveal a Wnt-dependent osteogenic mechanism, and they provide a potential target pathway for designing therapeutics to promote bone formation. |