Linked Life Data

21135136

Source:http://linkedlifedata.com/resource/pubmed/id/21135136

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pubmed-article:21135136pubmed:abstractTextSphingosine-1-phosphate (S1P), a lipid mediator enriched in blood, controls the dynamic migration of osteoclast (OC) precursors (OPs) between the blood and bone, in part via the S1P receptor 1 (S1PR1) which directs positive chemotaxis toward S1P. We show that OPs also express S1PR2, an S1P receptor which mediates negative chemotaxis (or chemorepulsion). OP-positive chemotaxis is prominent in gradients with low maximal concentrations of S1P, whereas such behavior is minimal in fields with high maximal S1P concentrations. This reverse-directional behavior is caused by S1PR2-mediated chemorepulsion acting to override S1PR1 upgradient motion. S1PR2-deficient mice exhibit moderate osteopetrosis as a result of a decrease in osteoclastic bone resorption, suggesting that S1PR2 contributes to OP localization on the bones mediated by chemorepulsion away from the blood where S1P levels are high. Inhibition of S1PR2 function by the antagonist JTE013 changed the migratory behavior of monocytoid cells, including OPs, and relieved osteoporosis in a mouse model by limiting OP localization and reducing the number of mature OCs attached to the bone surface. Thus, reciprocal regulation of S1P-dependent chemotaxis controls bone remodeling by finely regulating OP localization. This regulatory axis may be promising as a therapeutic target in diseases affecting OC-dependent bone remodeling.lld:pubmed
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pubmed-article:21135136pubmed:authorpubmed-author:IshiiMasaruMlld:pubmed
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pubmed-article:21135136pubmed:authorpubmed-author:ShimazuYutaka...lld:pubmed
pubmed-article:21135136pubmed:authorpubmed-author:KikutaJunichi...lld:pubmed
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pubmed-article:21135136pubmed:dateRevised2011-8-1lld:pubmed
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pubmed-article:21135136pubmed:articleTitleChemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo.lld:pubmed
pubmed-article:21135136pubmed:affiliationLaboratory of Biological Imaging, WPI-Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. mishii@ifrec.osaka-u.ac.jplld:pubmed
pubmed-article:21135136pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21135136pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:21135136pubmed:publicationTypeResearch Support, N.I.H., Intramurallld:pubmed
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