NFATc1在RANKL诱导破骨细胞激活中的调控机制。
Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation.
作者信息
Song Insun, Kim Jung Ha, Kim Kabsun, Jin Hye Mi, Youn Bang Ung, Kim Nacksung
机构信息
National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Brain Korea 21, Chonnam National University Medical School, 5 Hak-Dong, Dong-Ku, Gwangju 501-746, Republic of Korea.
出版信息
FEBS Lett. 2009 Jul 21;583(14):2435-40. doi: 10.1016/j.febslet.2009.06.047. Epub 2009 Jul 2.
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.
NFATc1是RANKL诱导破骨细胞分化的主要调节因子，在此我们研究NFATc1在破骨细胞激活中的调节机制。NFATc1的失活强烈减弱RANKL诱导的骨吸收，而在破骨细胞中组成型活性形式的NFATc1的过表达诱导牙本质切片上肌动蛋白环和吸收凹的形成。我们证明NFATc1直接结合其靶基因的启动子区域并诱导包括LTBP3、ClC7、组织蛋白酶K、MMP9和c-Src等各种基因的表达，这些基因是骨吸收的关键参与者。因此，NFATc1通过上调破骨细胞激活基因对RANKL诱导的破骨细胞激活至关重要。
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