The role of NFAT in osteoclast formation
The role of NFAT in osteoclast formation
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DOI：
10.1196/annals.1402.071
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Takayanagi, Hiroshi
中科院分区：
文献类型：
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作者：
Takayanagi, Hiroshi
破骨细胞是单核-巨噬细胞来源的细胞，其降解骨基质。在巨噬细胞集落刺激因子（M-CSF）和共刺激信号存在下，NF-κ B配体受体激活剂（RANKL）诱导破骨细胞形成。RANKL诱导TNF受体相关因子6（TRAF 6）和c-Fos通路的活化，这导致破骨细胞特异性事件，即活化T细胞核因子（NFAT）cl的自身扩增，NFAT cl是破骨细胞分化的主要转录因子。NFATc 1的自动扩增依赖于与免疫受体基于酪氨酸的激活基序（ITAM）相关的免疫球蛋白样受体的钙信号传导。除了钙调神经磷酸酶-NFATc 1轴外，钙信号还激活钙调蛋白依赖性激酶途径，该途径在破骨细胞形成中也起关键作用。破骨细胞分化的分子机制的理解的这些进展有望导致新的治疗方法，骨疾病。
Osteoclasts are cells of monocyte-macrophage origin that degrade bone matrix. Receptor activator of NF-kappa B ligand (RANKL) induces osteoclast formation in the presence of macrophage-colony-stimulating factor (M-CSF) and costimulatory signals. RANKL induces activation of the TNF receptor-associated factor 6 (TRAF6) and c-Fos pathways, which lead to the osteoclast-specific event, that is, autoamplification of nuclear factor of activated T cells (NFAT)cl, the master transcription factor for osteoclast differentiation. Autoamplification of NFATc1 is dependent on the calcium signaling of immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adaptors. In addition to the calcineurin-NFATc1 axis, calcium signaling activates the calmodulin-dependent kinase pathway, which also plays a critical role in osteoclast formation. Such advances in the understanding of the molecular mechanism of osteoclast differentiation are expected to lead to novel therapeutic approaches to bone diseases.