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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2001-1-22
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pubmed:abstractText |
While TNF-alpha is pivotal to the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are unknown. We find that a pure population of murine osteoclast precursors fails to undergo osteoclastogenesis when treated with TNF-alpha alone. In contrast, the cytokine dramatically stimulates differentiation in macrophages primed by less than one percent of the amount of RANKL (ligand for the receptor activator of NF-kappaB) required to induce osteoclast formation. Mirroring their synergistic effects on osteoclast differentiation, TNF-alpha and RANKL markedly potentiate NF-kappaB and stress-activated protein kinase/c-Jun NH(2)-terminal kinase activity, two signaling pathways essential for osteoclastogenesis. In vivo administration of TNF-alpha prompts robust osteoclast formation in chimeric animals in which ss-galactosidase positive, TNF-responsive macrophages develop within a TNF-nonresponsive stromal environment. Thus, while TNF-alpha alone does not induce osteoclastogenesis, it does so both in vitro and in vivo by directly targeting macrophages within a stromal environment that expresses permissive levels of RANKL. Given the minuscule amount of RANKL sufficient to synergize with TNF-alpha to promote osteoclastogenesis, TNF-alpha appears to be a more convenient target in arresting inflammatory osteolysis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10495128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10496522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10637272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10671521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10677500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10683372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10712423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10864917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10934644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-10968780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-1713625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-1874190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-2201703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-3805716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-7939685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-7989596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-8263720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-8442433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-8445302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-8545103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-8698454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-9108485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-9294124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-9792645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11120755-9794488
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
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, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1481-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11120755-Animals,
pubmed-meshheading:11120755-Bone Marrow Transplantation,
pubmed-meshheading:11120755-Carrier Proteins,
pubmed-meshheading:11120755-Cell Differentiation,
pubmed-meshheading:11120755-Cells, Cultured,
pubmed-meshheading:11120755-Drug Synergism,
pubmed-meshheading:11120755-Enzyme Activation,
pubmed-meshheading:11120755-Flow Cytometry,
pubmed-meshheading:11120755-Histocytochemistry,
pubmed-meshheading:11120755-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11120755-Macrophages,
pubmed-meshheading:11120755-Membrane Glycoproteins,
pubmed-meshheading:11120755-Mice,
pubmed-meshheading:11120755-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11120755-NF-kappa B,
pubmed-meshheading:11120755-Osteoclasts,
pubmed-meshheading:11120755-RANK Ligand,
pubmed-meshheading:11120755-Receptor Activator of Nuclear Factor-kappa B,
pubmed-meshheading:11120755-Stem Cells,
pubmed-meshheading:11120755-Tumor Necrosis Factor-alpha
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pubmed:year |
2000
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pubmed:articleTitle |
TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand.
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pubmed:affiliation |
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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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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