活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca2+相关协同刺激信号通路与Ca2+非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈诱导,在NFATc1转录过程中的启动、扩增及靶向作用三个阶段通过复杂交互的调节影响其下游各种靶基因及蛋白,最终介导破骨细胞的分化、融合及对无机和有机骨基质的降解作用。宏观上,NFATc1还受到外界机械应力的影响从而在破骨细胞生长过程中发挥作用;并且NFATc1的调节过程受其自身节律的影响。本文就NFATc1的结构、相关调节机制和对破骨细胞的作用研究进展进行综述。
Nuclear factor-activated T cell 1( NFATc1) is a crucial transcription factor in osteoclast,which is regulated by the induction of RANKL signaling pathways,the amplification of Ca2 +dependent costimulatory signal pathways and Ca2 +independent signal pathway,and the negative feedback induction of Lhx2/IRF8/Mafb/Bcl6 in the three phases of NFATc1 transcription( initiation,amplification and targeting). Whereafter,NFATc1 regulates downstream target genes and proteins to affect the differentiation and fusion of osteoclasts, and adjust the degradation of inorganic and organic bone matrix through complex interactions. Macroscopically,NFATc1 is also influenced by external mechanical stress to play a role in the osteoclast growth process. Meanwhile,NFATc1 has the special circadian expression rhythm. This article reviews the research progress on NFATc1 structure,regulation mechanism and its effect on osteoclasts.