rdf:type |
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lifeskim:mentions |
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pubmed:issue |
31
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pubmed:dateCreated |
2003-7-28
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pubmed:abstractText |
Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29130-5
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12759356-Animals,
pubmed-meshheading:12759356-Bone Morphogenetic Protein 2,
pubmed-meshheading:12759356-Bone Morphogenetic Proteins,
pubmed-meshheading:12759356-Cell Line,
pubmed-meshheading:12759356-Chondrocytes,
pubmed-meshheading:12759356-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:12759356-Gene Expression,
pubmed-meshheading:12759356-Growth Plate,
pubmed-meshheading:12759356-I-kappa B Proteins,
pubmed-meshheading:12759356-In Situ Hybridization,
pubmed-meshheading:12759356-Male,
pubmed-meshheading:12759356-Mice,
pubmed-meshheading:12759356-Mice, Knockout,
pubmed-meshheading:12759356-Mice, Transgenic,
pubmed-meshheading:12759356-Mutagenesis, Site-Directed,
pubmed-meshheading:12759356-NF-kappa B,
pubmed-meshheading:12759356-Promoter Regions, Genetic,
pubmed-meshheading:12759356-RNA, Messenger,
pubmed-meshheading:12759356-Response Elements,
pubmed-meshheading:12759356-Transforming Growth Factor beta,
pubmed-meshheading:12759356-beta-Galactosidase
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pubmed:year |
2003
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pubmed:articleTitle |
NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.
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pubmed:affiliation |
Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, Missouri 64108, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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