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dc.contributor.authorOwen, Thomas A.
dc.contributor.authorAronow, Michael A.
dc.contributor.authorShalhoub, Victoria
dc.contributor.authorBarone, Leesa M.
dc.contributor.authorWilming, Laurens G.
dc.contributor.authorTassinari, Melissa S.
dc.contributor.authorKennedy, Mary Beth
dc.contributor.authorPockwinse, Shirwin M.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.date2022-08-11T08:10:56.000
dc.date.accessioned2022-08-23T17:25:44Z
dc.date.available2022-08-23T17:25:44Z
dc.date.issued1990-06-01
dc.date.submitted2011-01-11
dc.identifier.citationJ Cell Physiol. 1990 Jun;143(3):420-30. <a href="http://dx.doi.org/10.1002/jcp.1041430304">Link to article on publisher's site</a>
dc.identifier.issn0021-9541 (Linking)
dc.identifier.doi10.1002/jcp.1041430304
dc.identifier.pmid1694181
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49471
dc.description.abstractThe relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes. Modifications in gene expression define a developmental sequence that has 1) three principle periods--proliferation, extracellular matrix maturation, and mineralization--and 2) two restriction points to which the cells can progress but cannot pass without further signals--the first when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle- and cell growth-regulated genes, produce a fibronectin/type I collagen extracellular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase immediately following the proliferative period, and later, an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited by hydroxyurea; and 3) enhanced levels of expression of the osteoblast markers as a function of ascorbic acid-induced collagen deposition, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and the development of the osteoblast phenotype.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=1694181&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcp.1041430304
dc.subjectAlkaline Phosphatase
dc.subjectAnimals
dc.subjectBone Development
dc.subjectCell Differentiation
dc.subjectCell Division
dc.subjectCollagen
dc.subjectDown-Regulation
dc.subjectExtracellular Matrix
dc.subjectGene Expression
dc.subjectHistocytochemistry
dc.subjectOsteoblasts
dc.subjectOsteopontin
dc.subjectPhenotype
dc.subjectRNA
dc.subjectRats
dc.subjectSialoglycoproteins
dc.subjectCell Biology
dc.titleProgressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix
dc.typeJournal Article
dc.source.journaltitleJournal of cellular physiology
dc.source.volume143
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/124
dc.identifier.contextkey1724168
html.description.abstract<p>The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes. Modifications in gene expression define a developmental sequence that has 1) three principle periods--proliferation, extracellular matrix maturation, and mineralization--and 2) two restriction points to which the cells can progress but cannot pass without further signals--the first when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle- and cell growth-regulated genes, produce a fibronectin/type I collagen extracellular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase immediately following the proliferative period, and later, an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited by hydroxyurea; and 3) enhanced levels of expression of the osteoblast markers as a function of ascorbic acid-induced collagen deposition, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and the development of the osteoblast phenotype.</p>
dc.identifier.submissionpathstein/124
dc.contributor.departmentDepartment of Orthopedic Surgery
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages420-30


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