TY - JOUR
T1 - Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation
AU - Tu, Xiaolin
AU - Joeng, Kyu Sang
AU - Nakayama, Keiichi I.
AU - Nakayama, Keiko
AU - Rajagopal, Jayaraj
AU - Carroll, Thomas J J.
AU - McMahon, Andrew P.
AU - Long, Fanxin
N1 - Funding Information:
We are indebted to Drs. Xi He, Walter Koch, Christopher Niehrs, Frank McCormick, and Steve Teitelbaum for providing reagents. We thank Drs. Deborah Stumpo and Perry Blackshear (NIEHS) for sharing MARCKS −/− mouse embryos. The work was supported in part by National Institutes of Health grants R01 DK065789 (F.L.) and P01 DK056246 (A.P.M.). K.S.J. was supported by the Korea Science and Engineering Foundation.
PY - 2007/1
Y1 - 2007/1
N2 - Wnt signaling regulates a variety of developmental processes in animals. Although the β-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 Gαq/11 subunits of G proteins to activate phosphatidylinositol signaling and PKCδ in the murine ST2 cells. Gαq/11-PKCδ signaling is required for Wnt3a-induced osteoblastogenesis in these cells, and PKCδ 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 PKCδ-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.
AB - Wnt signaling regulates a variety of developmental processes in animals. Although the β-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 Gαq/11 subunits of G proteins to activate phosphatidylinositol signaling and PKCδ in the murine ST2 cells. Gαq/11-PKCδ signaling is required for Wnt3a-induced osteoblastogenesis in these cells, and PKCδ 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 PKCδ-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.
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U2 - 10.1016/j.devcel.2006.11.003
DO - 10.1016/j.devcel.2006.11.003
M3 - Article
C2 - 17199045
AN - SCOPUS:33845802651
SN - 1534-5807
VL - 12
SP - 113
EP - 127
JO - Developmental Cell
JF - Developmental Cell
IS - 1
ER -