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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2008-7-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20948-58
pubmed:dateRevised
2008-11-21
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
pubmed:year
2008
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.
pubmed:affiliation
Stryker Biotech, 35 South Street, Hopkinton, MA 01748, USA.
pubmed:publicationType
Journal Article