NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1
NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1
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DOI：
10.1074/jbc.m610701200
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发表时间：
2007-06-22
影响因子：
4.8
通讯作者：
Boyce, Brendan F.
中科院分区：
文献类型：
--
作者：
Yamashita, Teruhito;Yao, Zhenqiang;Boyce, Brendan F.
nf - κ B配体受体激活剂（RANKL）和肿瘤坏死因子（TNF）诱导的破骨细胞形成和骨吸收增加是绝经后骨质疏松和类风湿关节破坏的原因。这些细胞因子诱导的破骨细胞形成需要NF-kappa B p50和p52、c-Fos和NFATc1在破骨细胞前体中的表达。c-Fos诱导NFATc1，但NF-kappa B与这些其他转录因子在破骨细胞发生中的关系尚不清楚。我们报道了当c-Fos或NFATc1表达时，RANKL和TNF可以直接诱导NF-kappa B p50/p52双敲除（dKO）破骨细胞前体形成破骨细胞。RANKL-或tnf诱导的c-Fos上调和激活在dKO细胞和nf - κ B抑制剂处理的野生型细胞中被消除。在dKO细胞中，c-Fos表达需要同时使用RANKL或TNF来诱导NFATc1活化。此外，c-Fos的表达增加了TNF诱导的野生型破骨细胞的数量和吸收能力。我们得出结论，NF-kappa B控制着由RANKL和TNF直接诱导的早期破骨细胞分化，导致c-Fos的激活，随后是NFATc1的激活。抑制nf - κ B可阻止RANKL-和tnf诱导的骨吸收。
Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-kappa B ligand (RANKL) and tumor necrosis factor (TNF). Osteoclast formation induced by these cytokines requires NF-kappa B p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors. c-Fos induces NFATc1, but the relationship between NF-kappa B and these other transcription factors in osteoclastogenesis remains poorly understood. We report that RANKL and TNF can induce osteoclast formation directly from NF-kappa B p50/p52 double knockout (dKO) osteoclast precursors when either c-Fos or NFATc1 is expressed. RANKL- or TNF-induced c-Fos up-regulation and activation are abolished in dKO cells and in wild-type cells treated with an NF-kappa B inhibitor. c-Fos expression requires concomitant RANKL or TNF treatment to induce NFATc1 activation in the dKO cells. Furthermore, c-Fos expression increases the number and resorptive capacity of wild-type osteoclasts induced by TNF in vitro. We conclude that NF-kappa B controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1. Inhibition of NF-kappa B should prevent RANKL- and TNF-induced bone resorption.