Regulatory mechanisms of Ca^<2+> oscillations and transcription factor NFAT in osteoclastogenesis.

核因子受体激活剂κB配体(RANKL)在破骨细胞分化(破骨细胞形成)过程中诱导Ca~(2+)振荡并激活活化T细胞核因子1(NFATc1)。Ca^&lt；2+&gt；振荡是破骨细胞发生的重要触发信号，然而，服务于Ca^&lt；2+&gt；振荡的Ca^&lt；2+&gt；通透性内流途径的分子基础尚未确定。利用DNA芯片，我们发现RANKL处理的RAW264.7细胞(破骨前细胞)与未处理的细胞相比，瞬时受体电位香草样通道2(TRPV2)显著表达。因此，我们进一步研究了TRPV2在钙离子振荡和破骨细胞生成中的表达和功能作用。综上所述，RANKL依赖的TRPV2和SOCE的激活以及细胞内钙离子的释放触发了破骨前细胞的钙振荡。随后NFATc1的激活促进了破骨细胞的形成。

The receptor activator of NFκB ligand (RANKL) induces Ca^<2+> oscillations and activates the Nuclear Factor of Activated T cells 1 (NFATc1) during osteoclast differentiation (osteoclastogenesis). Ca^<2+> oscillations are an important trigger signal for osteoclastogenesis, however the molecular basis of Ca^<2+> permeable influx pathways serving Ca^<2+> oscillations has not yet been identified. Using a DNA microarray, we found that Transient Receptor Potential Vanilloid channels 2 (TRPV2) are expressed significantly in RANKL-treated RAW264.7 cells (preosteoclasts) compared to untreated cells. Therefore, we further investigated the expression and functional role of TRPV2 on Ca^<2+> oscillations and osteoclastogenesis. In conclusion, Ca^<2+> oscillations in preosteoclasts are triggered by RANKL-dependent TRPV2 and SOCE activation and intracellular Ca^<2+> release. Subsequent activation of NFATc1 promotes osteoclastogenesis.