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Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213228/ https://www.ncbi.nlm.nih.gov/pubmed/16275763 http://dx.doi.org/10.1084/jem.20051150 |
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author | Asagiri, Masataka Sato, Kojiro Usami, Takako Ochi, Sae Nishina, Hiroshi Yoshida, Hiroki Morita, Ikuo Wagner, Erwin F. Mak, Tak W. Serfling, Edgar Takayanagi, Hiroshi |
author_facet | Asagiri, Masataka Sato, Kojiro Usami, Takako Ochi, Sae Nishina, Hiroshi Yoshida, Hiroki Morita, Ikuo Wagner, Erwin F. Mak, Tak W. Serfling, Edgar Takayanagi, Hiroshi |
author_sort | Asagiri, Masataka |
collection | PubMed |
description | NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1 (−/−) hematopoietic stem cells to osteoclast-deficient Fos (−/−) mice, and by Fos (−/−) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1 (−/−) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis. |
format | Text |
id | pubmed-2213228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22132282008-03-11 Autoamplification of NFATc1 expression determines its essential role in bone homeostasis Asagiri, Masataka Sato, Kojiro Usami, Takako Ochi, Sae Nishina, Hiroshi Yoshida, Hiroki Morita, Ikuo Wagner, Erwin F. Mak, Tak W. Serfling, Edgar Takayanagi, Hiroshi J Exp Med Article NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1 (−/−) hematopoietic stem cells to osteoclast-deficient Fos (−/−) mice, and by Fos (−/−) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1 (−/−) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis. The Rockefeller University Press 2005-11-07 /pmc/articles/PMC2213228/ /pubmed/16275763 http://dx.doi.org/10.1084/jem.20051150 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Asagiri, Masataka Sato, Kojiro Usami, Takako Ochi, Sae Nishina, Hiroshi Yoshida, Hiroki Morita, Ikuo Wagner, Erwin F. Mak, Tak W. Serfling, Edgar Takayanagi, Hiroshi Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title | Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title_full | Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title_fullStr | Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title_full_unstemmed | Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title_short | Autoamplification of NFATc1 expression determines its essential role in bone homeostasis |
title_sort | autoamplification of nfatc1 expression determines its essential role in bone homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213228/ https://www.ncbi.nlm.nih.gov/pubmed/16275763 http://dx.doi.org/10.1084/jem.20051150 |
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