Linked Life Data

15728181

Source:http://linkedlifedata.com/resource/pubmed/id/15728181

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pubmed-article:15728181pubmed:abstractTextDentin 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.lld:pubmed
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pubmed-article:15728181pubmed:authorpubmed-author:TurnerCharles...lld:pubmed
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pubmed-article:15728181pubmed:articleTitleDentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo.lld:pubmed
pubmed-article:15728181pubmed:affiliationDepartment of Periodontics and Cellular and Structural Biology, University of Texas, San Antonio, Texas 78229, USA.lld:pubmed
pubmed-article:15728181pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15728181pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:15728181pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:15728181pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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