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dc.contributor.authorLian, Jane B.
dc.contributor.authorShalhoub, Victoria
dc.contributor.authorAslam, Fauzia
dc.contributor.authorFrenkel, Baruch
dc.contributor.authorGreen, Jack
dc.contributor.authorHamrah, Michael
dc.contributor.authorStein, Gary S.
dc.contributor.authorStein, Janet L.
dc.date2022-08-11T08:10:02.000
dc.date.accessioned2022-08-23T16:52:54Z
dc.date.available2022-08-23T16:52:54Z
dc.date.issued1997-05-01
dc.date.submitted2008-07-09
dc.identifier.citation<p>Endocrinology. 1997 May;138(5):2117-27.</p>
dc.identifier.issn0013-7227 (Print)
dc.identifier.pmid9112412
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42150
dc.description.abstractThe mouse MC3T3-E1 cell line is nontumorigenic and undergoes a typical program of osteoblast differentiation in vitro, producing a bone-like mineralized extracellular matrix. We report responses of these cells to dexamethasone (Dex) and 1,25-(OH)2D3 that are in contrast to findings from other osteoblast culture systems. First, chronic exposure of both early- and late-passaged MC3T3-E1 cells to 10(-7) M Dex, initiated during the proliferation period, blocked osteoblast differentiation, in contrast to the enhanced differentiation observed in cultures of fetal rat calvarial-derived cells. Secondly, 1,25-(OH)2D3 did not up-regulate expression (messenger RNA or protein synthesis) of the endogenous mouse osteocalcin (OC) gene. Several lines of evidence are presented that suggest this response is caused by sequence specific properties of the mouse OC vitamin D response element. We also observed both qualitative and quantitative differences in expression of cell growth (histone H2B) and phenotype-related genes (collagen, OC, osteopontin, glucocorticoid receptor, and 1, 25-(OH)2D3 receptor), between pre- and postmineralization stage osteoblasts, in response to 24 h steroid hormone treatment. Our findings in MC3T3-E1 cells are consistent with current concepts of selective influences of 1,25-(OH)2D3 and glucocorticoids as a function of osteoblast maturation. However, the inhibition of osteoblast differentiation by chronic Dex at 10(-7) M and the down-regulation of OC by 1,25-(OH)2D3 are novel observations relevant to species-specific responsiveness of mouse bone-expressed genes to steroid hormones during osteoblast differentiation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9112412&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1210/en.138.5.2117
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCalcitriol
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectDexamethasone
dc.subjectGene Expression
dc.subjectGlucocorticoids
dc.subjectHistones
dc.subjectMice
dc.subjectOsteoblasts
dc.subjectOsteocalcin
dc.subjectPromoter Regions (Genetics)
dc.subjectRNA, Messenger
dc.subjectTime Factors
dc.subjectTransfection
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSpecies-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3-E1 osteoblasts: dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression
dc.typeArticle
dc.source.journaltitleEndocrinology
dc.source.volume138
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/523
dc.identifier.contextkey545005
html.description.abstract<p>The mouse MC3T3-E1 cell line is nontumorigenic and undergoes a typical program of osteoblast differentiation in vitro, producing a bone-like mineralized extracellular matrix. We report responses of these cells to dexamethasone (Dex) and 1,25-(OH)2D3 that are in contrast to findings from other osteoblast culture systems. First, chronic exposure of both early- and late-passaged MC3T3-E1 cells to 10(-7) M Dex, initiated during the proliferation period, blocked osteoblast differentiation, in contrast to the enhanced differentiation observed in cultures of fetal rat calvarial-derived cells. Secondly, 1,25-(OH)2D3 did not up-regulate expression (messenger RNA or protein synthesis) of the endogenous mouse osteocalcin (OC) gene. Several lines of evidence are presented that suggest this response is caused by sequence specific properties of the mouse OC vitamin D response element. We also observed both qualitative and quantitative differences in expression of cell growth (histone H2B) and phenotype-related genes (collagen, OC, osteopontin, glucocorticoid receptor, and 1, 25-(OH)2D3 receptor), between pre- and postmineralization stage osteoblasts, in response to 24 h steroid hormone treatment. Our findings in MC3T3-E1 cells are consistent with current concepts of selective influences of 1,25-(OH)2D3 and glucocorticoids as a function of osteoblast maturation. However, the inhibition of osteoblast differentiation by chronic Dex at 10(-7) M and the down-regulation of OC by 1,25-(OH)2D3 are novel observations relevant to species-specific responsiveness of mouse bone-expressed genes to steroid hormones during osteoblast differentiation.</p>
dc.identifier.submissionpathoapubs/523
dc.contributor.departmentUniversity of Massachusetts Medical Center Department of Cell Biology and Cancer Center
dc.source.pages2117-27


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