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dc.contributor.authorFrenkel, Baruch
dc.contributor.authorCapparelli, Casey
dc.contributor.authorVan Auken, Moira
dc.contributor.authorBaran, Daniel T.
dc.contributor.authorBryan, J.
dc.contributor.authorStein, Janet L.
dc.contributor.authorStein, Gary S.
dc.contributor.authorLian, Jane B.
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):2109-16.</p>
dc.identifier.issn0013-7227 (Print)
dc.identifier.pmid9112411
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42151
dc.description.abstractThe bone-specific osteocalcin gene is a well established marker of osteoblast activity. We have studied osteocalcin transcription in transgenic mice carrying rat osteocalcin promoter-chloramphenicol acetyltransferase (CAT) reporter constructs. Transgenic lines carrying each of the 1.7-, 1.1-, 0.72-, or 0.35-kilobase promoter constructs expressed the reporter gene in a tissue-specific manner. However, each of these constructs was sensitive to site of integration effects, reflected by a high frequency of nonexpressing transgenic lines. High expression of the 1.7-kilobase promoter in osseous tissues was accompanied by low ectopic expression in the brain. Analysis of CAT expression in femurs, calvariae, and lumbar vertebrae of this line indicated considerable variability in promoter activity among individual transgenic animals. Analysis of the variance in CAT activity demonstrated a linkage between promoter activities in these distant skeletal sites. Promoter activity was inversely correlated with age, and females exhibited severalfold higher activity than age-matched males. Bone marrow stromal cells from these animals, cultured under conditions that support osteoblast differentiation, exhibited the expected postproliferative onset of osteocalcin promoter activity, as assessed by CAT assay. The ex vivo CAT activity was not dependent on the sex or the age of the donor transgenic mouse. Taken together, our results are consistent with the hypothesis that a common, probably humoral, factor(s) regulates osteocalcin transcription in distant skeletal sites. We suggest that the abundance of this factor(s) is different between males and females and among individual mice at a given time point, and that ex vivo culturing of osteoblasts reduces the variation in osteocalcin promoter activity by eliminating the physiological contribution of this factor.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9112411&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1210/en.138.5.2109
dc.subjectAging
dc.subjectAnimals
dc.subjectBone Marrow Cells
dc.subjectBone and Bones
dc.subject*Cell Differentiation
dc.subjectCells, Cultured
dc.subjectChloramphenicol O-Acetyltransferase
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectOsteoblasts
dc.subjectOsteocalcin
dc.subject*Promoter Regions (Genetics)
dc.subjectSex Characteristics
dc.subjectStromal Cells
dc.subjectTransfection
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleActivity of the osteocalcin promoter in skeletal sites of transgenic mice and during osteoblast differentiation in bone marrow-derived stromal cell cultures: effects of age and sex
dc.typeArticle
dc.source.journaltitleEndocrinology
dc.source.volume138
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/524
dc.identifier.contextkey545006
html.description.abstract<p>The bone-specific osteocalcin gene is a well established marker of osteoblast activity. We have studied osteocalcin transcription in transgenic mice carrying rat osteocalcin promoter-chloramphenicol acetyltransferase (CAT) reporter constructs. Transgenic lines carrying each of the 1.7-, 1.1-, 0.72-, or 0.35-kilobase promoter constructs expressed the reporter gene in a tissue-specific manner. However, each of these constructs was sensitive to site of integration effects, reflected by a high frequency of nonexpressing transgenic lines. High expression of the 1.7-kilobase promoter in osseous tissues was accompanied by low ectopic expression in the brain. Analysis of CAT expression in femurs, calvariae, and lumbar vertebrae of this line indicated considerable variability in promoter activity among individual transgenic animals. Analysis of the variance in CAT activity demonstrated a linkage between promoter activities in these distant skeletal sites. Promoter activity was inversely correlated with age, and females exhibited severalfold higher activity than age-matched males. Bone marrow stromal cells from these animals, cultured under conditions that support osteoblast differentiation, exhibited the expected postproliferative onset of osteocalcin promoter activity, as assessed by CAT assay. The ex vivo CAT activity was not dependent on the sex or the age of the donor transgenic mouse. Taken together, our results are consistent with the hypothesis that a common, probably humoral, factor(s) regulates osteocalcin transcription in distant skeletal sites. We suggest that the abundance of this factor(s) is different between males and females and among individual mice at a given time point, and that ex vivo culturing of osteoblasts reduces the variation in osteocalcin promoter activity by eliminating the physiological contribution of this factor.</p>
dc.identifier.submissionpathoapubs/524
dc.contributor.departmentDepartment of Cell Biology and Cancer Center
dc.source.pages2109-16


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