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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.
Pubmed ID: 16275763
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Institution of higher education in the United States. Private Ivy League research university in Cambridge, Massachusetts.
View all literature mentionsAffymetrix has recently released a new software for the acquisition, management, and analysis of gene expression data. The new GeneChip Operating Software (GCOS) platform enables researchers to perform gene expression, SNP mapping and resequencing analysis with integrated data management and scalable client server configurations. * Compatible with additional Affymetrix analysis software such as Data Mining Tool (DMT) and GeneChip DNA Analysis Software (GDAS) * Supports Gene Expression, Resequencing and Genotyping Applications * Baseline Comparison Analysis Input: Affymetrix .DAT file Output: Affymetrix files (.CEL, .CHP, .RPT, .EXP, .TXT) Availability: The Core Facility has a copy of GCOS, as well as an older version of the Affymetrix software, Microarray Suite (MAS), available for use upon request.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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