During osteoclast differentiation, the expression of the transcription factor nuclear factor of activated T cell 1 (Nfatc1) increases in an autoproliferative manner. Nfatc1 isoforms are of three sizes, and only the short isoform increases during osteoclast differentiation. Genetic ablation of the whole Nfatc1 gene demonstrated that it is essential for osteoclastogenesis; however, the specific role of the Nfatc1 short form (Nfatc1/αA) remains unknown. In this study, we engineered Nfatc1 short form-specific knockout mice and found that these mice died in utero by day 13.5. We developed a novel osteoclast culture system in which hematopoietic stem cells were cultured, proliferated, and then differentiated into osteoclasts in vitro. Using this system, we show that the Nfatc1/αA isoform is essential for osteoclastogenesis and is responsible for the expression of various osteoclast markers, the Nfatc1 short form itself, and Nfatc1 regulators.

在破骨细胞分化过程中，活化 T 细胞转录因子核因子 1 (Nfatc1) 的表达以自身增殖方式增加。Nfatc1亚型有三种大小，只有短亚型在破骨细胞分化过程中增加。整个 Nfatc1 基因的基因消融表明它对于破骨细胞生成至关重要；然而，Nfatc1 短形式（Nfatc1/αA）的具体作用仍不清楚。在这项研究中，我们工程化了 Nfatc1 短型特异性敲除小鼠，发现这些小鼠在第 13.5 天时在子宫内死亡。我们开发了一种新型破骨细胞培养系统，其中造血干细胞在体外培养、增殖，然后分化为破骨细胞。使用该系统，我们表明 Nfatc1/αA 亚型对于破骨细胞生成至关重要，并负责各种破骨细胞标记物、Nfatc1 短形式本身和 Nfatc1 调节剂的表达。