Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
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DOI：
10.1016/j.bbrc.2005.01.117
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Takayanagi, R
中科院分区：
文献类型：
--
作者：
Ohnaka, K;Tanabe, M;Takayanagi, R
为了探讨糖皮质激素引起的骨质疏松的机制，我们研究了糖皮质激素对作为促进骨形成的一种新的关键途径的规范WRIT信号的影响。WNT3a增强原代培养人成骨细胞T细胞因子(Tcf)/淋巴增强因子(LEF)依赖的转录活性。地塞米松以剂量依赖的方式抑制这种转录活性，而1，25-二羟基维生素D3增加这种转录活性。糖原合成酶激酶-3β的抑制剂LiCl也能增强Tcf/Lef依赖的转录活性，但地塞米松不能抑制这一作用。抗Dickkopf-1抗体的加入部分恢复了地塞米松抑制的转录活性。地塞米松可降低WNT3a诱导的β-连环素的胞浆积累量，并抑制WNT3a诱导的β-连环素的核转位。这些数据表明，糖皮质激素抑制培养的人成骨细胞中的规范WRIT信号，部分是通过促进Dickkopf-1的产生。(C)2005 Elsevier Inc.保留所有权利。
To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Writ signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3beta, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of P-catenin accumulated by Wnt3a and also inhibited the nuclear translocation of beta-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Writ signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production. (C) 2005 Elsevier Inc. All rights reserved.