Source:http://linkedlifedata.com/resource/pubmed/id/17698843
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
43
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| pubmed:dateCreated |
2007-10-22
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| pubmed:abstractText |
Growth hormone (GH) affects bone size and mass in part through stimulating insulin-like growth factor type 1 (IGF-1) production in liver and bone. Whether GH acts independent of IGF-1 in bone remains unclear. To define the mode of GH action in bone, we have used a Cre/loxP system in which the type 1 IGF-1 receptor (Igf1r) has been disrupted specifically in osteoblasts in vitro and in vivo. Calvarial osteoblasts from mice homozygous for the floxed IGF-1R allele (IGF-1R(flox/flox)) were infected with adenoviral vectors expressing Cre. Disruption of IGF-1R mRNA (>90%) was accompanied by near elimination of IGF-1R protein but retention of GHR protein. GH-induced STAT5 activation was consistently greater in osteoblasts with an intact IGF-1R. Osteoblasts lacking IGF-1R retained GH-induced ERK and Akt phosphorylation and GH-stimulated IGF-1 and IGFBP-3 mRNA expression. GH-induced osteoblast proliferation was abolished by Cre-mediated disruption of the IGF-1R or co-incubation of cells with an IGF-1-neutralizing antibody. By contrast, GH inhibited apoptosis in osteoblasts lacking the IGF-1R. To examine the effects of GH on osteoblasts in vivo, mice wild type for the IGF-1R treated with GH subcutaneously for 7 days showed a doubling in the number of osteoblasts lining trabecular bone, whereas osteoblast numbers in similarly treated mice lacking the IGF-1R in osteoblasts were not significantly affected. These results indicate that although direct IGF-1R-independent actions of GH on osteoblast apoptosis can be demonstrated in vitro, IGF-1R is required for anabolic effects of GH in osteoblasts in vivo.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
26
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| pubmed:volume |
282
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
31666-74
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17698843-Adenoviridae,
pubmed-meshheading:17698843-Alleles,
pubmed-meshheading:17698843-Animals,
pubmed-meshheading:17698843-Animals, Newborn,
pubmed-meshheading:17698843-Apoptosis,
pubmed-meshheading:17698843-Cell Proliferation,
pubmed-meshheading:17698843-Cells, Cultured,
pubmed-meshheading:17698843-Female,
pubmed-meshheading:17698843-Genetic Vectors,
pubmed-meshheading:17698843-Green Fluorescent Proteins,
pubmed-meshheading:17698843-Growth Hormone,
pubmed-meshheading:17698843-Injections, Subcutaneous,
pubmed-meshheading:17698843-Mice,
pubmed-meshheading:17698843-Mice, Transgenic,
pubmed-meshheading:17698843-Models, Biological,
pubmed-meshheading:17698843-Osteoblasts,
pubmed-meshheading:17698843-RNA, Messenger,
pubmed-meshheading:17698843-Receptor, IGF Type 1,
pubmed-meshheading:17698843-Signal Transduction,
pubmed-meshheading:17698843-Skull,
pubmed-meshheading:17698843-Time Factors
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| pubmed:year |
2007
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| pubmed:articleTitle |
Mode of growth hormone action in osteoblasts.
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| pubmed:affiliation |
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
|