Source:http://linkedlifedata.com/resource/pubmed/id/21542012
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2011-5-4
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| pubmed:abstractText |
Bone morphogenetic protein 2 (BMP-2) plays a critical role in the differentiation of precursor cells and has been approved for clinical application to induce new bone formation. To date, unexpectedly high doses of recombinant BMP-2 have been required to induce bone healing in humans. Thus, enhancing cellular responsiveness to BMP-2 potentially has critically important clinical implications. BMP responsiveness may be modulated in part by cross-talk with other signaling pathways, including mitogen-activated protein kinases (MAPKs). c-Jun NH(2)-terminal kinase (JNK) is a MAPK that has been reported to be required for late-stage differentiation of preosteoblasts and BMP-2-induced differentiation of preosteoblasts and pleuripotent cells. In this study we determined that MC3T3-E1-clone 24?cells (MC-24) can be induced by BMP-2 to differentiate into mineralizing osteoblast cultures. Using this inducible system, we employed both JNK loss-of-function and gain-of-function reagents to make three key observations: (1) JNK is required for phosphorylation of Smad1 by BMP-2 and subsequent activation of Smad1 signaling and osteoblast differentiation, (2) JNK1, but not JNK2, is required for BMP-2-induced formation of mineralized nodules, and (3) JNK1 activation decreases binding of inhibitory Smad6 to the type I BMP receptor (BMPR-I) and reciprocally increases binding of Smad1, both observations that would increase responsiveness to BMP-2. Understanding this and other pathways that lead to increased cellular responsiveness to BMPs could greatly aid more cost-effective and safe clinical delivery of these important molecules.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Smad1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad6 Protein
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| pubmed:status |
MEDLINE
|
| pubmed:month |
May
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| pubmed:issn |
1523-4681
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 American Society for Bone and Mineral Research.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
26
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1122-32
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| pubmed:meshHeading |
pubmed-meshheading:21542012-Animals,
pubmed-meshheading:21542012-Bone Morphogenetic Protein 2,
pubmed-meshheading:21542012-Bone Morphogenetic Protein Receptors, Type I,
pubmed-meshheading:21542012-Calcification, Physiologic,
pubmed-meshheading:21542012-Cell Differentiation,
pubmed-meshheading:21542012-Cell Line,
pubmed-meshheading:21542012-Cell Nucleus,
pubmed-meshheading:21542012-Enzyme Activation,
pubmed-meshheading:21542012-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:21542012-Mice,
pubmed-meshheading:21542012-Osteoblasts,
pubmed-meshheading:21542012-Phosphorylation,
pubmed-meshheading:21542012-Protein Binding,
pubmed-meshheading:21542012-Rats,
pubmed-meshheading:21542012-Rats, Sprague-Dawley,
pubmed-meshheading:21542012-Smad1 Protein,
pubmed-meshheading:21542012-Smad6 Protein,
pubmed-meshheading:21542012-Transcription, Genetic
|
| pubmed:year |
2011
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| pubmed:articleTitle |
Activation of c-Jun NH(2)-terminal kinase 1 increases cellular responsiveness to BMP-2 and decreases binding of inhibitory Smad6 to the type 1 BMP receptor.
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| pubmed:affiliation |
Atlanta Veterans Affairs Medical Center and Department of Orthopaedics, Emory University School of Medicine, Decatur, GA, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|