Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation

Xiaolin Tu, Kyu Sang Joeng, Keiichi I. Nakayama, Keiko Nakayama, Jayaraj Rajagopal, Thomas J J. Carroll, Andrew P. McMahon, Fanxin Long

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)113-127
Number of pages15
JournalDevelopmental Cell
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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