Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation
Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation
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DOI：
10.1016/j.febslet.2009.06.047
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发表时间：
2009-07-21
期刊：
影响因子：
3.5
通讯作者：
Kim, Nacksung
中科院分区：
文献类型：
--
作者：
Song, Insun;Kim, Jung Ha;Kim, Nacksung
NFATc1是RANKL诱导的破骨细胞分化的主要调节因子，本文研究了NFATc1在破骨细胞活化中的调节机制。NFATc1的失活强烈减弱RANKL诱导的骨吸收，破骨细胞中NFATc1组成型活性形式的过表达诱导牙本质切片上肌动蛋白环和吸收陷窝的形成。我们证明，NFATc1直接结合到其靶基因的启动子区，并诱导各种基因的表达，包括LTBP3，ClC7，组织蛋白酶K，MMP 9和c-Src，这是骨吸收的关键球员。因此，NFATc1通过上调破骨细胞活化基因对RANKL诱导的破骨细胞活化至关重要。(C)2009年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
NFATc1 is a master regulator of RANKL-induced osteoclast differentiation and herein we investigate the regulatory mechanism of NFATc1 in osteoclast activation. Inactivation of NFATc1 strongly attenuates RANKL-induced bone resorption and overexpression of a constitutively active form of NFATc1 in osteoclasts induces formation of actin rings and resorption pits on dentin slices. We demonstrate that NFATc1 binds directly to the promoter regions of its target genes and induces expression of various genes, including LTBP3, ClC7, cathepsin K, MMP9, and c-Src, which are key players in bone resorption. Thus, NFATc1 is essential for RANKL-induced osteoclast activation via up-regulation of osteoclast-activating genes. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.