Noncanonical Wnt signaling through G protein-linked PKCδ activation promotes bone formation
Noncanonical Wnt signaling through G protein-linked PKCδ activation promotes bone formation
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DOI：
10.1016/j.devcel.2006.11.003
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发表时间：
2007-01-01
影响因子：
11.8
通讯作者：
Long, Fanxin
中科院分区：
文献类型：
--
作者：
Tu, Xiaolin;Joeng, Kyu Sang;Long, Fanxin
Wnt信号调节动物的多种发育过程。虽然已知β-连环蛋白依赖性（经典）途径控制细胞命运，但在哺乳动物中尚未建立非经典Wnt信号传导的类似作用。此外，非经典Wnt信号转导的细胞内级联仍有待阐明。在这里，我们描绘了一个途径，其中Wnt 3a信号通过G蛋白的G α（q/11）亚基激活磷脂酰肌醇信号和PKC δ在小鼠ST 2细胞。G alpha（q/11）-PKC delta信号传导是Wnt 3a诱导的这些细胞中成骨细胞生成所必需的，并且PKC delta纯合突变小鼠在胚胎骨形成中表现出缺陷。此外，体内成骨细胞表达的Wnt 7 b通过PKC δ介导的途径在体外诱导成骨细胞分化;骨骼祖细胞中Wnt 7 b的消融导致小鼠胚胎中的骨减少。总之，这些结果揭示了Wnt依赖性成骨机制，并且它们为设计促进骨形成的治疗方法提供了潜在的靶向途径。
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 G alpha(q/11) subunits of G proteins to activate phosphatidylinositol signaling and PKC delta in the murine ST2 cells. G alpha(q/11)-PKC delta signaling is required for Wnt3a-induced osteoblastogenesis in these cells, and PKC delta 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 PKC delta-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.