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

Department of Medicine, Washington University Medical School, St. Louis, MO 63110, USA.
Developmental Cell (Impact Factor: 9.71). 02/2007; 12(1):113-27. DOI: 10.1016/j.devcel.2006.11.003
Source: PubMed


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.

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Available from: Xiaolin Tu, Feb 12, 2014
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    • "In particular, Wnt7b and Wnt10b are postulated to play the significant important roles in the process of bone mass control (Kubota et al. 2010). Mice with mutations of the Wnt7b and Wnt10b genes presented with impaired osteogenesis and slower bone growth rate respectively (Bennett et al. 2007, Tu et al. 2007). However, it also is worth mentioning two other members of the Wnt superfamily, namely Wnt1 and Wnt16, which have recently been revealed to play an important role in either the bone formation or repression of osteoclastogenesis and the prevention of cortical bone fragility fractures respectively (Laine et al. 2013, Moverare-Skrtic et al. 2014). "
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    • "Approximately 2 weeks after the cultivation, cells were fixed. These cells were stained with alizarin red S or stained for alkaline phosphatase activity as described previously33. Mineralized area (%) in wells was calculated using NIH image software. "
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