Source:http://linkedlifedata.com/resource/pubmed/id/17531955
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-7-2
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pubmed:abstractText |
Strontium ranelate has several beneficial effects on bone and reduces the risk of vertebral and hip fractures in women with postmenopausal osteoporosis. We investigated whether Sr(2+) acts via a cell surface calcium-sensing receptor (CaR) in HEK293 cells stably transfected with the bovine CaR (HEK-CaR) and rat primary osteoblasts (POBs) expressing the CaR endogenously. Elevating Ca(o)(2+) or Sr(2+) concentration-dependently activated the CaR in HEK-CaR but not in non-transfected cells, but the potency of Sr(2+) varied depending on the biological response tested. Sr(2+) was less potent than Ca(o)(2+) in stimulating inositol phosphate accumulation and in increasing Ca(i)(2+), but was comparable to Ca(o)(2+) in stimulating ERK phosphorylation and a non-selective cation channel, suggesting that Ca(2+) and Sr(2+) have differential effects on specific cellular processes. With physiological concentrations of Ca(o)(2+), Sr(2+)-induced further CaR activation. Neither Sr(2+) nor Ca(o)(2+) affected the four parameters just described in non-transfected cells. In POB, Sr(2+) stimulated cellular proliferation. This effect was CaR-mediated, as transfecting the cells with a dominant negative bovine CaR significantly attenuated Ca(o)(2+)-stimulated POB proliferation. Finally, Sr(2+) significantly increased the mRNA levels of the immediate early genes, c-fos and egr-1, which are involved in POB proliferation, and this effect was attenuated by overexpressing the dominant negative CaR. In conclusion, Sr(2+) is a full CaR agonist in HEK-CaR and POB, and, therefore, the anabolic effect of Sr(2+) on bone in vivo could be mediated, in part, by the CaR.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcium-Sensing,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/strontium ranelate
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
438-47
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17531955-Animals,
pubmed-meshheading:17531955-Base Sequence,
pubmed-meshheading:17531955-Calcium,
pubmed-meshheading:17531955-Cell Line,
pubmed-meshheading:17531955-Cell Proliferation,
pubmed-meshheading:17531955-DNA Primers,
pubmed-meshheading:17531955-Humans,
pubmed-meshheading:17531955-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17531955-Organometallic Compounds,
pubmed-meshheading:17531955-Osteoblasts,
pubmed-meshheading:17531955-Patch-Clamp Techniques,
pubmed-meshheading:17531955-Polymerase Chain Reaction,
pubmed-meshheading:17531955-Rats,
pubmed-meshheading:17531955-Rats, Sprague-Dawley,
pubmed-meshheading:17531955-Receptors, Calcium-Sensing,
pubmed-meshheading:17531955-Thiophenes
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pubmed:year |
2007
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pubmed:articleTitle |
The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation.
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pubmed:affiliation |
Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. Naibedya@cdriindia.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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