Canonical Wnt signaling in osteoblasts is required for osteoclast differentiation
Canonical Wnt signaling in osteoblasts is required for osteoclast differentiation
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DOI：
10.1196/annals.1346.015
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Karsenty, Gerard
中科院分区：
文献类型：
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作者：
Glass, Donald A., II;Karsenty, Gerard
Lrp 5（一种编码可能的Wnt共受体的基因）的失活通过减少骨形成而导致低骨量（骨质减少），这表明成骨细胞中的Wnt信号传导调节骨形成。在这里，我们表明，Tcf 1和Tcf 4在成骨细胞在发育过程中和出生后表达;稳定的β-连环蛋白，一个典型的Wnt信号的重要组成部分，在分化的成骨细胞的结果在高骨量，而其删除从分化的成骨细胞导致骨质减少。组织学分析表明，这些突变影响骨吸收。细胞和分子研究表明，β-连环蛋白与TCF蛋白一起调节成骨细胞中骨保护素的表达，骨保护素是破骨细胞分化的主要抑制剂。这些研究结果表明，在分化的成骨细胞中，P-连环蛋白和可能的Wnt信号是破骨细胞分化的负调节因子;因此，它们拓宽了我们对Wnt蛋白在骨骼发生的各个阶段可能具有的功能的认识。
Inactivation of Lrp5, a gene encoding a likely Wnt co-receptor, results in low bone mass (osteopenia) by decreasing bone formation, suggesting that Wnt signaling in osteoblasts regulates bone formation. Here we show that Tcf1 and Tcf4 are expressed in osteoblasts during development and after birth; stabilization of beta-catenin, an essential component of canonical Wnt signaling, in differentiated osteoblasts results in high bone mass while its deletion from differentiated osteoblasts leads to osteopenia. Histological analysis showed that these mutations affect bone resorption. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates in osteoblasts the expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that, in differentiated osteoblasts, P-catenin and presumably Wnt signaling are negative regulators of osteoclast differentiation; thus they broaden our knowledge about functions that Wnt proteins may have at various stages of skeletogenesis.