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Publication : Essentiality of Nfatc1 short isoform in osteoclast differentiation and its self-regulation.

First Author  Omata Y Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  18797
PubMed ID  37914750 Mgi Jnum  J:342901
Mgi Id  MGI:7546462 Doi  10.1038/s41598-023-45909-3
Citation  Omata Y, et al. (2023) Essentiality of Nfatc1 short isoform in osteoclast differentiation and its self-regulation. Sci Rep 13(1):18797
abstractText  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/alphaA) 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/alphaA isoform is essential for osteoclastogenesis and is responsible for the expression of various osteoclast markers, the Nfatc1 short form itself, and Nfatc1 regulators.
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