Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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.
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:issnType
Print
pubmed:day
27
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20680-90
pubmed:dateRevised
2007-11-14
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