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 Carroll, Andrew P. McMahon, Fanxin Long

Research output: Contribution to journalArticle

210 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 (US)
Pages (from-to)113-127
Number of pages15
JournalDevelopmental Cell
Volume12
Issue number1
DOIs
StatePublished - Jan 2007

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GTP-Binding Proteins
Osteogenesis
Bone
Chemical activation
Catenins
Phosphatidylinositols
Osteoblasts
Mammals
Ablation
Embryonic Structures
Animals
Bone and Bones
Therapeutics

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation. / Tu, Xiaolin; Joeng, Kyu Sang; Nakayama, Keiichi I.; Nakayama, Keiko; Rajagopal, Jayaraj; Carroll, Thomas J; McMahon, Andrew P.; Long, Fanxin.

In: Developmental Cell, Vol. 12, No. 1, 01.2007, p. 113-127.

Research output: Contribution to journalArticle

Tu, X, Joeng, KS, Nakayama, KI, Nakayama, K, Rajagopal, J, Carroll, TJ, McMahon, AP & Long, F 2007, 'Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation', Developmental Cell, vol. 12, no. 1, pp. 113-127. https://doi.org/10.1016/j.devcel.2006.11.003
Tu, Xiaolin ; Joeng, Kyu Sang ; Nakayama, Keiichi I. ; Nakayama, Keiko ; Rajagopal, Jayaraj ; Carroll, Thomas J ; McMahon, Andrew P. ; Long, Fanxin. / Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation. In: Developmental Cell. 2007 ; Vol. 12, No. 1. pp. 113-127.
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