rdf:type |
|
lifeskim:mentions |
umls-concept:C0011429,
umls-concept:C0017337,
umls-concept:C0029432,
umls-concept:C0033684,
umls-concept:C0205276,
umls-concept:C0331858,
umls-concept:C0443254,
umls-concept:C0871261,
umls-concept:C1515655,
umls-concept:C1533691,
umls-concept:C1704632,
umls-concept:C1704640,
umls-concept:C1706515,
umls-concept:C1706817,
umls-concept:C1708715,
umls-concept:C1880022,
umls-concept:C2346689,
umls-concept:C2911692
|
pubmed:issue |
21
|
pubmed:dateCreated |
2005-5-23
|
pubmed:abstractText |
Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is mechanically responsive. To study osteocyte-specific and mechanically regulated DMP1 gene expression, the transcriptional activity of three cis-regulatory regions was first examined in an osteoblast differentiation model in vitro using a green fluorescent protein (GFP) reporter. Expression of the -9624 to +1996 bp (10 kb) and -7892 to +4439 bp (8 kb) DMP1 cis-regulatory regions dramatically increased in areas of mineralized matrix, in dendritic, osteocyte-like cells. Mineralizing cultures expressing the 8-kb construct show dramatic GFP increases in response to loading in cells with a dendritic morphology. Transgenic mice expressing the 8-kb DMP1-GFP and -2433 to +4439 bp (2.5 kb) DMP1-LacZ were generated. Osteocyte-specific expression was found with the 8 kb but not with the 2.5 kb in postnatal animals. However, the 2.5 kb could support expression in rapidly forming osteoblasts and pre-osteocytes in the embryo. Primary calvarial osteoblast cultures demonstrated that the 2.5 kb supports weak expression in a subset of osteoblasts and pre-osteocytes, but not in mature osteocytes. However, the 8 kb supports robust expression in primary bone marrow cultures. Therefore the region -7892 to -2433 bp, termed a 5.5-kb "Osteocyte Enhancer Module," appears to be required for osteocyte specificity. Ulnae of mice with the 8-kb DMP1-GFP were subjected to mechanical loading where GFP expression increased selectively and locally in osteocytes, distal to the mid-shaft and near the surface of the bone. Thus, the 8-kb region of the DMP1 gene is a target for mechanotransduction in osteocytes, and its cis-regulatory activity may be correlated to local strain in bone.
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pubmed:grant |
|
pubmed:keyword |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0021-9258
|
pubmed:author |
pubmed-author:BonewaldLynda FLF,
pubmed-author:FengJian QJQ,
pubmed-author:Gluhak-HeinrichJelicaJ,
pubmed-author:GuoDayongD,
pubmed-author:HarrisMarie AMA,
pubmed-author:HarrisStephen ESE,
pubmed-author:KalajzicIvoI,
pubmed-author:KothaShivaS,
pubmed-author:LuYongboY,
pubmed-author:RoblingAlexander GAG,
pubmed-author:RoweDavid WDW,
pubmed-author:TurnerCharles HCH,
pubmed-author:YangWuchenW
|
pubmed:issnType |
Print
|
pubmed:day |
27
|
pubmed:volume |
280
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
20680-90
|
pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15728181-Animals,
pubmed-meshheading:15728181-Biomechanics,
pubmed-meshheading:15728181-Bone Marrow Cells,
pubmed-meshheading:15728181-Bone and Bones,
pubmed-meshheading:15728181-Cell Differentiation,
pubmed-meshheading:15728181-Cell Line,
pubmed-meshheading:15728181-Extracellular Matrix Proteins,
pubmed-meshheading:15728181-Gene Expression Regulation,
pubmed-meshheading:15728181-Green Fluorescent Proteins,
pubmed-meshheading:15728181-Humans,
pubmed-meshheading:15728181-Mechanotransduction, Cellular,
pubmed-meshheading:15728181-Mice,
pubmed-meshheading:15728181-Mice, Transgenic,
pubmed-meshheading:15728181-Osteoblasts,
pubmed-meshheading:15728181-Osteocytes,
pubmed-meshheading:15728181-Phosphoproteins,
pubmed-meshheading:15728181-Recombinant Fusion Proteins,
pubmed-meshheading:15728181-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:15728181-Stress, Mechanical,
pubmed-meshheading:15728181-Transfection,
pubmed-meshheading:15728181-Ulna,
pubmed-meshheading:15728181-beta-Galactosidase
|
pubmed:year |
2005
|
pubmed:articleTitle |
Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo.
|
pubmed:affiliation |
Department of Periodontics and Cellular and Structural Biology, University of Texas, San Antonio, Texas 78229, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|