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dc.contributor.authorSchepmoes, Grace
dc.contributor.authorBreen, Ellen C.
dc.contributor.authorOwen, Thomas A.
dc.contributor.authorAronow, Michael A.
dc.contributor.authorStein, Gary S.
dc.contributor.authorLian, Jane B.
dc.date2022-08-11T08:10:56.000
dc.date.accessioned2022-08-23T17:25:41Z
dc.date.available2022-08-23T17:25:41Z
dc.date.issued1991-10-01
dc.date.submitted2011-01-11
dc.identifier.citationJ Cell Biochem. 1991 Oct;47(2):184-96. <a href="http://dx.doi.org/10.1002/jcb.240470212">Link to article on publisher's site</a>
dc.identifier.issn0730-2312 (Linking)
dc.identifier.doi10.1002/jcb.240470212
dc.identifier.pmid1757481
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49459
dc.description.abstractThe influence of dexamethasone on expression of the osteocalcin gene which encodes the most abundant non-collagenous and only reported bone-specific protein was examined in ROS 17/2.8 osteosarcoma cells which express a broad spectrum of genes related to bone formation. Consistent with previous reports, quantitation of cellular osteocalcin mRNA levels by Northern blot analysis, osteocalcin gene transcription by activity of the osteocalcin gene promoter fused to a chloramphenicol acetyl-transferase (CAT) mRNA coding sequence following transfection into ROS 17/2.8 cells, and osteocalcin biosynthesis by radioimmunoassay indicate that dexamethasone in a concentration range of 10(-6) to 10(-9) M only modestly modifies basal levels of osteocalcin gene expression. However, dexamethasone significantly inhibits these parameters of the vitamin D-induced upregulation of osteocalcin gene expression in both proliferating and in confluent ROS 17/2.8 cells. In this study, we observed that the extent to which abrogation of the vitamin D response occurs is dependent on basal levels of osteocalcin gene expression as reflected by a complete inhibition of the vitamin D-induced upregulation in a ROS 17/2.8K subline with low basal expression and only a partial reduction of the vitamin D stimulation in a ROS 17/2.8C subline with eightfold higher levels of basal expression. This effect of glucocorticoid appears to be at the transcriptional and post-transcriptional levels as demonstrated by a parallel decline in the cellular representation of osteocalcin mRNA, osteocalcin gene promoter activity, and osteocalcin biosynthesis. The complexity of the glucocorticoid effect on vitamin D-mediated transcriptional properties of the osteocalcin gene is indicated by persistence of sequence-specific protein-DNA interactions at two principal osteocalcin gene promoter regulatory elements, the osteocalcin (CCAAT) box which modulates basal level of transcription, and the vitamin D responsive element, where vitamin D-mediated enhancement of osteocalcin gene transcription is controlled.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=1757481&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcb.240470212
dc.subjectBlotting, Northern
dc.subjectCell Differentiation
dc.subjectDNA-Binding Proteins
dc.subjectDexamethasone
dc.subjectElectrophoresis, Polyacrylamide Gel
dc.subject*Gene Expression Regulation
dc.subjectGlucocorticoids
dc.subjectHumans
dc.subjectOsteocalcin
dc.subjectOsteosarcoma
dc.subjectRNA, Messenger
dc.subjectRNA, Neoplasm
dc.subjectRadioimmunoassay
dc.subjectTranscription, Genetic
dc.subjectTumor Cells, Cultured
dc.subjectUp-Regulation
dc.subjectVitamin D
dc.subjectCell Biology
dc.titleInfluence of dexamethasone on the vitamin D-mediated regulation of osteocalcin gene expression
dc.typeJournal Article
dc.source.journaltitleJournal of cellular biochemistry
dc.source.volume47
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/113
dc.identifier.contextkey1724157
html.description.abstract<p>The influence of dexamethasone on expression of the osteocalcin gene which encodes the most abundant non-collagenous and only reported bone-specific protein was examined in ROS 17/2.8 osteosarcoma cells which express a broad spectrum of genes related to bone formation. Consistent with previous reports, quantitation of cellular osteocalcin mRNA levels by Northern blot analysis, osteocalcin gene transcription by activity of the osteocalcin gene promoter fused to a chloramphenicol acetyl-transferase (CAT) mRNA coding sequence following transfection into ROS 17/2.8 cells, and osteocalcin biosynthesis by radioimmunoassay indicate that dexamethasone in a concentration range of 10(-6) to 10(-9) M only modestly modifies basal levels of osteocalcin gene expression. However, dexamethasone significantly inhibits these parameters of the vitamin D-induced upregulation of osteocalcin gene expression in both proliferating and in confluent ROS 17/2.8 cells. In this study, we observed that the extent to which abrogation of the vitamin D response occurs is dependent on basal levels of osteocalcin gene expression as reflected by a complete inhibition of the vitamin D-induced upregulation in a ROS 17/2.8K subline with low basal expression and only a partial reduction of the vitamin D stimulation in a ROS 17/2.8C subline with eightfold higher levels of basal expression. This effect of glucocorticoid appears to be at the transcriptional and post-transcriptional levels as demonstrated by a parallel decline in the cellular representation of osteocalcin mRNA, osteocalcin gene promoter activity, and osteocalcin biosynthesis. The complexity of the glucocorticoid effect on vitamin D-mediated transcriptional properties of the osteocalcin gene is indicated by persistence of sequence-specific protein-DNA interactions at two principal osteocalcin gene promoter regulatory elements, the osteocalcin (CCAAT) box which modulates basal level of transcription, and the vitamin D responsive element, where vitamin D-mediated enhancement of osteocalcin gene transcription is controlled.</p>
dc.identifier.submissionpathstein/113
dc.contributor.departmentDepartment of Surgery
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages184-96


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