[PDF][PDF] Noncanonical Wnt signaling through G protein-linked PKCδ activation promotes bone formation

X Tu, KS Joeng, KI Nakayama, K Nakayama… - Developmental cell, 2007 - cell.com
X Tu, KS Joeng, KI Nakayama, K Nakayama, J Rajagopal, TJ Carroll, AP McMahon, F Long
Developmental cell, 2007cell.com
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 Gα q/11 subunits of G proteins to
activate phosphatidylinositol signaling and PKCδ in the murine ST2 cells. Gα q/11-PKCδ …
Summary
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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