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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2005-10-17
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pubmed:abstractText |
Osteoclast differentiation from hematopoietic precursors is controlled by the tumor necrosis factor family member tumor necrosis factor-related activation-induced cytokine (TRANCE) via induction of various transcription factors, including nuclear factor of activated T cells (NFAT) c1. During osteoclast differentiation, NFATc1 is further activated via calcium signaling when costimulatory receptors expressed on osteoclast precursors, such as osteoclast-associated receptor (OSCAR), are stimulated. Here we show that NFATc1 expression precedes that of OSCAR during TRANCE-mediated osteoclastogenesis and that inhibition of NFATc1 by cyclosporin A abolishes TRANCE-induced OSCAR expression and subsequent osteoclast differentiation. Moreover, we show that the 1.0-kb promoter region of the OSCAR gene contains three potential NFATc1-binding sites. Induction of an OSCAR promoter-luciferase reporter is significantly increased when transiently transfected into 293T cells in combination with NFATc1 expression plasmid. Deletion and site-directed mutant constructs confirmed that NFATc1-binding sites are both functional and NFATc1-specific. Furthermore, NFATc1 synergistically activates an OSCAR reporter construct together with microphthalmia transcription factor and PU.1, transcription factors previously shown to be critical for osteoclast differentiation. In addition, a plasmid expressing constitutively active MAP kinase kinase 6 enhances the transactivation activity of NFATc1/microphthalmia transcription factor/PU.1 on the OSCAR promoter. Taken together, our results indicate that NFATc1 is an important transcription factor in the induction of OSCAR during osteoclastogenesis. Elucidation of NFATc1 as a transcription factor for OSCAR expression implies the presence of a positive feedback circuit of TRANCE-induced activation of NFATc1, involving NFATc1-mediated OSCAR expression and its subsequent activation of NFATc1, necessary for efficient differentiation of osteoclasts.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microphthalmia-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/OSCAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Oscar protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf11a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35209-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16109714-Animals,
pubmed-meshheading:16109714-Base Sequence,
pubmed-meshheading:16109714-Binding Sites,
pubmed-meshheading:16109714-Blotting, Northern,
pubmed-meshheading:16109714-Blotting, Western,
pubmed-meshheading:16109714-Bone Marrow Cells,
pubmed-meshheading:16109714-Carrier Proteins,
pubmed-meshheading:16109714-Cell Differentiation,
pubmed-meshheading:16109714-Cell Line,
pubmed-meshheading:16109714-Chromatin Immunoprecipitation,
pubmed-meshheading:16109714-Cyclosporine,
pubmed-meshheading:16109714-Cytokines,
pubmed-meshheading:16109714-Gene Deletion,
pubmed-meshheading:16109714-Gene Expression Regulation,
pubmed-meshheading:16109714-Genetic Vectors,
pubmed-meshheading:16109714-Humans,
pubmed-meshheading:16109714-Luciferases,
pubmed-meshheading:16109714-MAP Kinase Kinase 6,
pubmed-meshheading:16109714-Membrane Glycoproteins,
pubmed-meshheading:16109714-Mice,
pubmed-meshheading:16109714-Microphthalmia-Associated Transcription Factor,
pubmed-meshheading:16109714-Molecular Sequence Data,
pubmed-meshheading:16109714-Mutagenesis, Site-Directed,
pubmed-meshheading:16109714-Mutation,
pubmed-meshheading:16109714-NFATC Transcription Factors,
pubmed-meshheading:16109714-Plasmids,
pubmed-meshheading:16109714-Promoter Regions, Genetic,
pubmed-meshheading:16109714-Protein Binding,
pubmed-meshheading:16109714-Protein Biosynthesis,
pubmed-meshheading:16109714-Proto-Oncogene Proteins,
pubmed-meshheading:16109714-RANK Ligand,
pubmed-meshheading:16109714-Receptor Activator of Nuclear Factor-kappa B,
pubmed-meshheading:16109714-Receptors, Cell Surface,
pubmed-meshheading:16109714-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16109714-Trans-Activators,
pubmed-meshheading:16109714-Transcriptional Activation,
pubmed-meshheading:16109714-Transfection,
pubmed-meshheading:16109714-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis.
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pubmed:affiliation |
Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, 501-746, Korea.
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pubmed:publicationType |
Journal Article
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