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dc.contributor.authorOwen, Thomas A.
dc.contributor.authorAronow, Michael A.
dc.contributor.authorBarone, Leesa M.
dc.contributor.authorBettencourt, B.
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.issued1991-03-01
dc.date.submitted2011-01-11
dc.identifier.citationEndocrinology. 1991 Mar;128(3):1496-504.
dc.identifier.issn0013-7227 (Linking)
dc.identifier.pmid1999168
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49462
dc.description.abstractNormal rat osteoblasts in culture undergo a developmental sequence consisting of a proliferation period in which high levels of the histone and collagen type I genes are expressed, followed by periods of matrix maturation [high levels of alkaline phosphatase (AP)] and mineralization that signal a high level of production of osteopontin (OP) and osteocalcin (OC). Since these parameters are regulated by vitamin D, the effects of both short term and chronic treatment with 1,25-dihydroxyvitamin D3 were examined during osteoblast growth and differentiation. In acute studies, during the proliferation period, histone mRNA (reflecting DNA synthesis) was inhibited (20-60%). Matrix Gla protein (MGP) and OP mRNA were significantly elevated during proliferation (30- and 15-fold), in contrast to OC which is not expressed and was not induced by hormone treatment. OP and MGP remained stimulated throughout the developmental sequence, but to a lesser degree (from 6- to 10-fold). Collagen and AP mRNA were inhibited by hormone at their peak levels of expression, but were stimulated at their lowest basal levels in the mineralization period. OC expression, which was initiated at the onset of mineralization, was stimulated 13- to 15-fold when basal levels were low, then from 6- to 8-fold by hormone throughout its period of expression. In chronic studies a different profile of gene expression was observed. When hormone treatment was initiated during the proliferation period on day 6, type I collagen and AP expression were suppressed, mineralized nodules did not develop, and induced levels of OP and OC gene expression did not occur. When chronic treatment was initiated on day 20 after the development of a mineralized matrix, OC, but not collagen and OP, levels were stimulated by the hormone. This observation is consistent with the requirement of a competent or mineralized bone matrix for expression of OC. In contrast, MGP expression was stimulated in the chronic vitamin D-treated cultures similar to acute treatments. Taken together these studies demonstrate that vitamin D, a physiological mediator of bone formation and remodelling, can both positively and negatively regulate expression of osteoblast phenotypic markers as a function of duration of hormone treatment and basal levels of gene expression, which is a reflection of bone matrix competency and the differentiated state of the osteoblast.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=1999168&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://endo.endojournals.org/cgi/reprint/128/3/1496
dc.subjectAnimals
dc.subjectBone Matrix
dc.subjectCell Differentiation
dc.subjectCell Division
dc.subjectCells, Cultured
dc.subject*Gene Expression Regulation
dc.subjectOsteoblasts
dc.subjectPhenotype
dc.subjectProteins
dc.subjectRats
dc.subjectReference Values
dc.subjectTime Factors
dc.subjectVitamin D
dc.subjectCell Biology
dc.titlePleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures
dc.typeJournal Article
dc.source.journaltitleEndocrinology
dc.source.volume128
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/116
dc.identifier.contextkey1724160
html.description.abstract<p>Normal rat osteoblasts in culture undergo a developmental sequence consisting of a proliferation period in which high levels of the histone and collagen type I genes are expressed, followed by periods of matrix maturation [high levels of alkaline phosphatase (AP)] and mineralization that signal a high level of production of osteopontin (OP) and osteocalcin (OC). Since these parameters are regulated by vitamin D, the effects of both short term and chronic treatment with 1,25-dihydroxyvitamin D3 were examined during osteoblast growth and differentiation. In acute studies, during the proliferation period, histone mRNA (reflecting DNA synthesis) was inhibited (20-60%). Matrix Gla protein (MGP) and OP mRNA were significantly elevated during proliferation (30- and 15-fold), in contrast to OC which is not expressed and was not induced by hormone treatment. OP and MGP remained stimulated throughout the developmental sequence, but to a lesser degree (from 6- to 10-fold). Collagen and AP mRNA were inhibited by hormone at their peak levels of expression, but were stimulated at their lowest basal levels in the mineralization period. OC expression, which was initiated at the onset of mineralization, was stimulated 13- to 15-fold when basal levels were low, then from 6- to 8-fold by hormone throughout its period of expression. In chronic studies a different profile of gene expression was observed. When hormone treatment was initiated during the proliferation period on day 6, type I collagen and AP expression were suppressed, mineralized nodules did not develop, and induced levels of OP and OC gene expression did not occur. When chronic treatment was initiated on day 20 after the development of a mineralized matrix, OC, but not collagen and OP, levels were stimulated by the hormone. This observation is consistent with the requirement of a competent or mineralized bone matrix for expression of OC. In contrast, MGP expression was stimulated in the chronic vitamin D-treated cultures similar to acute treatments. Taken together these studies demonstrate that vitamin D, a physiological mediator of bone formation and remodelling, can both positively and negatively regulate expression of osteoblast phenotypic markers as a function of duration of hormone treatment and basal levels of gene expression, which is a reflection of bone matrix competency and the differentiated state of the osteoblast.</p>
dc.identifier.submissionpathstein/116
dc.contributor.departmentDepartment of Orthopedic Surgery
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages1496-504


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