Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
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DOI：
10.1016/j.devcel.2005.02.017
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Karsenty, G
中科院分区：
文献类型：
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作者：
Glass, DA;Bialek, P;Karsenty, G
间充质祖细胞中p-catenin的失活阻止了成骨细胞的分化；编码可能的Wnt辅助受体的基因LRP5的失活通过减少骨形成而导致骨量减少(骨量减少)。这些观察表明，Wnt信号控制成骨细胞的分化，并提示它可能调节分化的成骨细胞的骨形成。在这里，我们研究了后来的事件，发现β-连环素在分化的成骨细胞中稳定会导致高骨量，而它从分化的成骨细胞中缺失会导致骨量减少。令人惊讶的是，组织学分析显示，这些突变主要影响骨吸收，而不是骨形成。细胞和分子研究表明，β-连环蛋白和TCF蛋白一起调节成骨细胞的骨保护素的表达，骨保护素是破骨细胞分化的主要抑制因子。这些发现表明，β-连环蛋白，以及可能的Wnt信号，促进了分化的成骨细胞抑制破骨细胞分化的能力；因此，它们拓宽了我们对Wnt蛋白在骨骼形成不同阶段的功能的认识。
Inactivation of p-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.