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首页> 外文期刊>Cell metabolism >TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts.
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TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts.

机译：TRPV4介导的钙内流调节破骨细胞的终末分化。

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摘要

Calcium signaling controls multiple cellular functions and is regulated by the release from internal stores and entry from extracellular fluid. In bone, osteoclast differentiation is induced by RANKL (receptor activator of NF-kappaB ligand)-evoked intracellular Ca(2+) oscillations, which trigger nuclear factor-activated T cells (NFAT) c1-responsive gene transcription. However, the Ca(2+) channels involved remain largely unidentified. Here we show that genetic ablation in mice of Trpv4, a Ca(2+)-permeable channel of the transient receptor potential (TRP) family, increases bone mass by impairing bone resorption. TRPV4 mediates basolateral Ca(2+) influx specifically in large osteoclasts when Ca(2+) oscillations decline. TRPV4-mediated Ca(2+) influx hereby secures intracellular Ca(2+) concentrations, ensures NFATc1-regulated gene transcription, and regulates the terminal differentiation and activity of osteoclasts. In conclusion, our data indicate that Ca(2+) oscillations and TRPV4-mediated Ca(2+) influx are sequentially required to sustain NFATc1-dependent gene expression throughout osteoclast differentiation, and we propose TRPV4 as a therapeutic target for bone diseases.
机译：钙信号传导控制多种细胞功能，并受内部储存物的释放和细胞外液的进入的调节。在骨中，破骨细胞分化是由RANKL（NF-κB配体的受体激活剂）引起的细胞内Ca（2+）振荡诱导的，该振荡触发核因子激活的T细胞（NFAT）c1反应基因转录。但是，所涉及的Ca（2+）通道在很大程度上仍未确定。在这里，我们显示Trpv4，瞬时受体电位（TRP）家族的Ca（2+）渗透通道的小鼠中的遗传消融，通过削弱骨吸收来增加骨量。 TRPV4介导大外侧破骨细胞时Ca（2+）振荡下降时基底外侧Ca（2+）流入。 TRPV4介导的Ca（2+）涌入从而确保细胞内Ca（2+）的浓度，确保NFATc1调控的基因转录，并​​调节破骨细胞的终末分化和活性。总之，我们的数据表明Ca（2+）振荡和TRPV4介导的Ca（2+）大量涌入是维持整个破骨细胞分化过程中维持NFATc1依赖性基因表达的先决条件，我们建议TRPV4作为骨疾病的治疗靶标。

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