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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2004-6-14
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pubmed:abstractText |
Osteoclasts are specialized macrophages that resorb bone. Mice lacking the AP-1 component c-Fos are osteopetrotic because of a lack of osteoclast differentiation and show an increased number of macrophages. The nature of the critical function of c-Fos in osteoclast differentiation is not known. Microarray analysis revealed that Nfatc1, another key regulator of osteoclastogenesis, was down-regulated in Fos(-/-) osteoclast precursors. Chromatin immunoprecipitation assay showed that c-Fos bound to the Nfatc1 and Acp5 promoters in osteoclasts. In vitro promoter analyses identified nuclear factor of activated T-cells (NFAT)/AP-1 sites in the osteoclast-specific Acp5 and Calcr promoters. Moreover, in Fos(-/-) precursors gene transfer of an active form of NFAT restored transcription of osteoclast-specific genes in the presence of receptor activator of the NF-kappaB ligand (RANKL), rescuing bone resorption. In the absence of RANKL, however, Fos(-/-) precursors were insensitive to NFAT-induced osteoclastogenesis unlike wild-type precursors. These data indicate that lack of Nfatc1 expression is the cause of the differentiation block in Fos(-/-) osteoclast precursors and that transcriptional induction of Nfatc1 is a major function of c-Fos in osteoclast differentiation.
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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/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nfatc1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nfatc2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear...,
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/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AburataniHiroyukiH,
pubmed-author:AmanoHitoshiH,
pubmed-author:BachlerMarcus AMA,
pubmed-author:GalsonDeborah LDL,
pubmed-author:IshikawaHiromichiH,
pubmed-author:LaplaceCatherineC,
pubmed-author:MatsuoKoichiK,
pubmed-author:PengLanL,
pubmed-author:WagnerErwin FEF,
pubmed-author:WangKent Z QKZ,
pubmed-author:ZhaoChenC
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26475-80
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pubmed:dateRevised |
2010-6-25
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pubmed:meshHeading |
pubmed-meshheading:15073183-Animals,
pubmed-meshheading:15073183-Blotting, Western,
pubmed-meshheading:15073183-Carrier Proteins,
pubmed-meshheading:15073183-Cell Differentiation,
pubmed-meshheading:15073183-Chromatin,
pubmed-meshheading:15073183-Coculture Techniques,
pubmed-meshheading:15073183-DNA-Binding Proteins,
pubmed-meshheading:15073183-Down-Regulation,
pubmed-meshheading:15073183-Gene Transfer Techniques,
pubmed-meshheading:15073183-Humans,
pubmed-meshheading:15073183-Macrophages,
pubmed-meshheading:15073183-Membrane Glycoproteins,
pubmed-meshheading:15073183-Mice,
pubmed-meshheading:15073183-Microscopy, Fluorescence,
pubmed-meshheading:15073183-NFATC Transcription Factors,
pubmed-meshheading:15073183-Nuclear Proteins,
pubmed-meshheading:15073183-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:15073183-Osteoclasts,
pubmed-meshheading:15073183-Precipitin Tests,
pubmed-meshheading:15073183-Promoter Regions, Genetic,
pubmed-meshheading:15073183-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:15073183-RANK Ligand,
pubmed-meshheading:15073183-Receptor Activator of Nuclear Factor-kappa B,
pubmed-meshheading:15073183-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15073183-Swine,
pubmed-meshheading:15073183-Transcription, Genetic,
pubmed-meshheading:15073183-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos.
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pubmed:affiliation |
Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160-8582, Japan. matsuo@sc.itc.keio.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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