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

NFκB配体受体激活因子（RANKL）在破骨细胞分化（破骨细胞生成）过程中诱导Ca^2+振荡并激活活化T细胞核因子1（NFATc 1）。Ca^2+振荡是破骨细胞生成的重要触发信号，然而，Ca ^2+渗透性内流途径中起作用的Ca ^2+振荡的分子基础尚未确定。使用DNA微阵列，我们发现瞬时受体电位香草酸通道2（TRPV2）在RANKL处理的RAW 264.7细胞（前破骨细胞）中的表达与未处理的细胞相比显着。因此，我们进一步研究了TRPV 2在Ca^2+振荡和破骨细胞生成中的表达和功能作用。总之，前破骨细胞中的Ca^2+振荡是由RANKL依赖的TRPV 2和SOCE激活以及细胞内Ca^2+释放触发的。随后NFATc1的激活促进破骨细胞生成。

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.