Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation
Copyright policy )Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation
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.
- Kyushu University Japan
- The University of Texas Southwestern Medical Center United States
- University of Mary United States
- WASHINGTON UNIVERSITY
- Department of Medicine Italy
Dishevelled Proteins, DEVBIO, Phosphatidylinositols, Bone and Bones, Mice, Osteogenesis, Animals, Myristoylated Alanine-Rich C Kinase Substrate, Adaptor Proteins, Signal Transducing, Glycoproteins, Osteoblasts, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Membrane Proteins, Cell Differentiation, Embryo, Mammalian, Enzyme Activation, SIGNALING, Culture Media, Conditioned, GTP-Binding Protein alpha Subunits, Gq-G11, Intercellular Signaling Peptides and Proteins, Gene Deletion, Developmental Biology
Dishevelled Proteins, DEVBIO, Phosphatidylinositols, Bone and Bones, Mice, Osteogenesis, Animals, Myristoylated Alanine-Rich C Kinase Substrate, Adaptor Proteins, Signal Transducing, Glycoproteins, Osteoblasts, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Membrane Proteins, Cell Differentiation, Embryo, Mammalian, Enzyme Activation, SIGNALING, Culture Media, Conditioned, GTP-Binding Protein alpha Subunits, Gq-G11, Intercellular Signaling Peptides and Proteins, Gene Deletion, Developmental Biology
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