Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-1-22
pubmed:abstractText
Macrophages differentiate into osteoclasts in response to the critical cytokine RANKL. However, the efficiency of RANKL-mediated osteoclastogenesis can be profoundly influenced by various cytokines. While studies describing the isolated effects of particular cytokines on osteoclastogenesis have been performed, combinatorial effects of cytokines have not been addressed routinely due to the absence of an efficient assay system. To study the effects of cytokine combinations on osteoclast formation, we performed in vitro assays using either the RAW293 cell line or primary murine splenic macrophages as osteoclast precursors. Using a multiparameter cytokine plating method, we analyzed osteoclastogenesis in response to multiple combinations of the following inflammation-related cytokines: RANKL, IFN-gamma, TNF-alpha, IL-1beta, IL-6, IL-10. We further investigated the role of T-cell-related cytokine combinations on osteoclastogenesis by measuring osteoclast area in response to RANKL with IFN-gamma, IL-2, IL-4, IL-6, TGF-ss, and TNF-alpha. Treatments with RANKL, TNF-alpha, and TGF-ss induced maximal osteoclast formation, suggesting a role for these cytokines in the most aggressive forms of inflammatory bone loss. TNF-alpha alone, however, was unable to induce osteoclast formation in the absence of RANKL despite co-administration of other proinflammatory cytokines. IFN-gamma was a potent inhibitor under all conditions, implicating T cells and NK cells in osteoclast inhibition. These studies demonstrate a rapid screening approach for identifying the potential collective effects of multiple factors on osteoclastic bone resorption.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acid Phosphatase, http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, 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/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/tartrate-resistant acid phosphatase
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0171-967X
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
584-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14517717-Acid Phosphatase, pubmed-meshheading:14517717-Animals, pubmed-meshheading:14517717-Biological Markers, pubmed-meshheading:14517717-Carrier Proteins, pubmed-meshheading:14517717-Combinatorial Chemistry Techniques, pubmed-meshheading:14517717-Drug Combinations, pubmed-meshheading:14517717-Isoenzymes, pubmed-meshheading:14517717-Macrophages, pubmed-meshheading:14517717-Membrane Glycoproteins, pubmed-meshheading:14517717-Mice, pubmed-meshheading:14517717-Mice, Inbred C57BL, pubmed-meshheading:14517717-Osteoclasts, pubmed-meshheading:14517717-RANK Ligand, pubmed-meshheading:14517717-Receptor Activator of Nuclear Factor-kappa B, pubmed-meshheading:14517717-Spleen, pubmed-meshheading:14517717-Transforming Growth Factor alpha, pubmed-meshheading:14517717-Transforming Growth Factor beta
pubmed:year
2003
pubmed:articleTitle
A rapid multiparameter approach to study factors that regulate osteoclastogenesis: demonstration of the combinatorial dominant effects of TNF-alpha and TGF-ss in RANKL-mediated osteoclastogenesis.
pubmed:affiliation
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.