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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-12-31
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pubmed:abstractText |
NFATc1 has been characterized as a master regulator of nuclear factor kappaB ligand-induced osteoclast differentiation. Herein, we demonstrate a novel role for NFATc1 as a positive regulator of nuclear factor kappaB ligand-mediated osteoclast fusion as well as other fusion-inducing factors such as TNF-alpha. Exogenous overexpression of a constitutively active form of NFATc1 in bone marrow-derived monocyte/macrophage cells (BMMs) induces formation of multinucleated osteoclasts as well as the expression of fusion-mediating molecules such as the d2 isoform of vacuolar ATPase V(o) domain (Atp6v0d2) and the dendritic cell-specific transmembrane protein (DC-STAMP). Moreover, inactivation of NFATc1 by cyclosporin A treatment attenuates expression of Atp6v0d2 and DC-STAMP and subsequent fusion process of osteoclasts. We show that NFATc1 binds to the promoter regions of Atp6v0d2 and DC-STAMP in osteoclasts and directly induces their expression. Furthermore, overexpression of Atp6v0d2 and DC-STAMP rescues cell-cell fusion of preosteoclasts despite reduced NFATc1 activity. Our data indicate for the first time that the NFATc1/Atp6v0d2 and DC-STAMP signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-10341023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-10368775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-10637272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-10968780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-11805147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-11807816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-12479813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-12695521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-12748652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-12796480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-12897775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-14722106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-15085135,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-15578568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-15695591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-16061724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-16109714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-16147974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-16275763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-16280328,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17885208-9774638
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
176-85
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17885208-Animals,
pubmed-meshheading:17885208-Blotting, Western,
pubmed-meshheading:17885208-Cell Differentiation,
pubmed-meshheading:17885208-Cell Fusion,
pubmed-meshheading:17885208-Dendritic Cells,
pubmed-meshheading:17885208-Membrane Proteins,
pubmed-meshheading:17885208-Mice,
pubmed-meshheading:17885208-NFATC Transcription Factors,
pubmed-meshheading:17885208-Nerve Tissue Proteins,
pubmed-meshheading:17885208-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:17885208-Osteoclasts,
pubmed-meshheading:17885208-Promoter Regions, Genetic,
pubmed-meshheading:17885208-Protein Binding,
pubmed-meshheading:17885208-Proton-Translocating ATPases,
pubmed-meshheading:17885208-RANK Ligand,
pubmed-meshheading:17885208-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2008
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pubmed:articleTitle |
NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP).
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pubmed:affiliation |
National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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