Source:http://linkedlifedata.com/resource/pubmed/id/18436533
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
30
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pubmed:dateCreated |
2008-7-21
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pubmed:abstractText |
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily of growth factors and are used clinically to induce new bone formation. The purpose of this study was to evaluate receptor utilization by BMP-2, BMP-4, BMP-6, and BMP-7 in primary human mesenchymal stem cells (hMSC), a physiologically relevant cell type that probably mediates the in vivo effects of BMPs. RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. BMPR1B and ACVR2B were expressed at low levels and were not found to play a significant role in signaling by any of the BMPs evaluated in this study. Type II receptor utilization differed significantly between BMP-2/4 and BMP-6/7. A greater reliance on BMPR2 was observed for BMP-2/4 relative to BMP-6/7, whereas ACVR2A was more critical to signaling by BMP-6/7 than BMP-2/4. Significant differences were also observed for the type I receptors. Although BMP-2/4 used predominantly BMPR1A for signaling, ACVR1A was the preferred type I receptor for BMP-6/7. Signaling by both BMP-2/4 and BMP-6/7 was mediated by homodimers of ACVR1A or BMPR1A. A portion of BMP-2/4 signaling also required concurrent BMPR1A and ACVR1A expression, suggesting that BMP-2/4 signal in part through ACVR1A/BMPR1A heterodimers. The capacity of ACVR1A and BMPR1A to form homodimers and heterodimers was confirmed by bioluminescence resonance energy transfer analyses. These results suggest different mechanisms for BMP-2/4- and BMP-6/7-induced osteoblastic differentiation in primary hMSC.
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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/BMP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BMP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BMP6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BMP7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 6,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 7,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20948-58
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18436533-Bone Marrow Cells,
pubmed-meshheading:18436533-Bone Morphogenetic Protein 2,
pubmed-meshheading:18436533-Bone Morphogenetic Protein 4,
pubmed-meshheading:18436533-Bone Morphogenetic Protein 6,
pubmed-meshheading:18436533-Bone Morphogenetic Protein 7,
pubmed-meshheading:18436533-Bone Morphogenetic Proteins,
pubmed-meshheading:18436533-Cell Differentiation,
pubmed-meshheading:18436533-Cell Membrane,
pubmed-meshheading:18436533-Dimerization,
pubmed-meshheading:18436533-Gene Expression Regulation,
pubmed-meshheading:18436533-Humans,
pubmed-meshheading:18436533-Mesenchymal Stem Cells,
pubmed-meshheading:18436533-Models, Biological,
pubmed-meshheading:18436533-Osteoblasts,
pubmed-meshheading:18436533-Signal Transduction,
pubmed-meshheading:18436533-Tissue Distribution,
pubmed-meshheading:18436533-Transforming Growth Factor beta
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pubmed:year |
2008
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pubmed:articleTitle |
BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells.
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pubmed:affiliation |
Stryker Biotech, 35 South Street, Hopkinton, MA 01748, USA.
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pubmed:publicationType |
Journal Article
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