Research article summary (published 30 Dec 2006):

Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation.

Full Abstract

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.

Author information

Author/s: Tu, Xiaolin (X); Joeng, Kyu Sang (KS); Nakayama, Keiichi I (KI); Nakayama, Keiko (K); Rajagopal, Jayaraj (J); Carroll, Thomas J (TJ); McMahon, Andrew P (AP); Long, Fanxin (F);

Affiliation: Department of Medicine, Washington University Medical School, St. Louis, MO 63110, USA.

Grants: P01 DK056246 (Agency:NIDDK NIH HHS) ; R01 DK065789 (Agency:NIDDK NIH HHS) ; R01 DK065789-03 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Developmental cell (Dev Cell), published in United States. (Language: eng)

Reference: 2007-Jan; vol 12 (issue 1) : pp 113-27

Dates: Created 2007/01/02; Completed 2007/02/16; Revised 2008/11/20;

PMID: 17199045, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptor Proteins, Signal Transducing - metabolism Animals Bone and Bones - abnormalities; embryology Cell Differentiation Culture Media, Conditioned Embryo, Mammalian - abnormalities; cytology Enzyme Activation GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism Gene Deletion Gene Expression Regulation, Developmental Glycoproteins - deficiency; metabolism Intercellular Signaling Peptides and Proteins - metabolism Intracellular Signaling Peptides and Proteins - metabolism

Membrane Proteins - metabolism Mice Osteoblasts - cytology Osteogenesis - physiology Phosphatidylinositols - metabolism Phosphoproteins - metabolism Phosphorylation Protein Kinase C-delta - metabolism Proto-Oncogene Proteins - deficiency; metabolism RNA, Messenger - genetics; metabolism Signal Transduction Wnt Proteins - deficiency; genetics; metabolism beta Catenin - metabolism

Associated Chemicals: Adaptor Proteins, Signal Transducing (0) ; Culture Media, Conditioned (0) ; Dkk1 protein, mouse (0) ; Glycoproteins (0) ; Intercellular Signaling Peptides and Proteins (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; Phosphatidylinositols (0) ; Phosphoproteins (0) ; Proto-Oncogene Proteins (0) ; RNA, Messenger (0) ; Wnt Proteins (0) ; Wnt-3 protein (0) ; Wnt7b protein, mouse (0) ; beta Catenin (0) ; dishevelled proteins (0) ; myristoylated alanine-rich C kinase substrate (125267-21-2) ; Protein Kinase C-delta (EC 2.7.1.37) ; GTP-Binding Protein alpha Subunits, Gq-G11 (EC 3.6.1.46)

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