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dc.contributor.authorStein, Gary S.
dc.contributor.authorLian, Jane B.
dc.contributor.authorGerstenfeld, Louis C.
dc.contributor.authorShalhoub, Victoria
dc.contributor.authorAronow, Michael A.
dc.contributor.authorOwen, Thomas A.
dc.contributor.authorMarkose, Elizabeth R.
dc.date2022-08-11T08:10:56.000
dc.date.accessioned2022-08-23T17:25:45Z
dc.date.available2022-08-23T17:25:45Z
dc.date.issued1989-01-01
dc.date.submitted2011-01-14
dc.identifier.citationConnect Tissue Res. 1989;20(1-4):3-13.
dc.identifier.issn0300-8207 (Linking)
dc.identifier.pmid2612161
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49477
dc.description.abstractThe relationship of proliferation to the developmental sequence associated with bone cell differentiation was examined in primary osteoblast cultures derived from fetal rat and embryonic chick calvaria. A reciprocal and functional relationship exists between the decline in proliferative activity which occurs during the initial stages of the developmental sequence and the induction of genes encoding osteoblast phenotype proteins associated with matrix maturation and mineralization. This relationship is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase (AP) and osteopontin (OP) genes immediately following the proliferative period and expression of osteocalcin with the onset of mineralization, and 2) increases in AP and OP when DNA synthesis is inhibited. By determining cellular mRNA levels and rates of mRNA synthesis in isolated nuclei, we found that the down-regulation of cell growth-related genes is modified at both the levels of transcription and mRNA stability. For a histone gene where down-regulation is transcriptionally mediated, we have observed that the shutdown of osteoblast proliferation is associated with the selective loss of the interaction of a promoter binding factor (HiNF-D) with a proximal regulatory element (Site II). A relationship between Site II occupancy by HiNF-D and the onset of osteoblast differentiation is supported by the persistence of Site II-HiNF-D interactions when proliferating rat osteoblasts are growth arrested under conditions that do not induce differentiation; and additionally, by the loss of Site II-HiNF-D interactions during the shut-down of proliferation when HL60 promyelocytic leukemia cells are induced to differentiate into monocytes. Our results are consistent with a requirement of proliferation for expression of genes involved with production, deposition and possibly organization of the osteoblast extracellular matrix. It is also reasonable to postulate that properties of the mineralizing matrix are related to the shut-down of proliferation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=2612161&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.3109/03008208909023869
dc.subjectAnimals
dc.subjectCell Differentiation
dc.subjectCell Division
dc.subjectCells, Cultured
dc.subjectChick Embryo
dc.subjectDown-Regulation
dc.subjectGene Expression
dc.subjectOsteoblasts
dc.subjectPhenotype
dc.subjectProtein Biosynthesis
dc.subjectRats
dc.subjectSkull
dc.subjectCell Biology
dc.titleThe onset and progression of osteoblast differentiation is functionally related to cellular proliferation
dc.typeJournal Article
dc.source.journaltitleConnective tissue research
dc.source.volume20
dc.source.issue1-4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/131
dc.identifier.contextkey1728436
html.description.abstract<p>The relationship of proliferation to the developmental sequence associated with bone cell differentiation was examined in primary osteoblast cultures derived from fetal rat and embryonic chick calvaria. A reciprocal and functional relationship exists between the decline in proliferative activity which occurs during the initial stages of the developmental sequence and the induction of genes encoding osteoblast phenotype proteins associated with matrix maturation and mineralization. This relationship is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phosphatase (AP) and osteopontin (OP) genes immediately following the proliferative period and expression of osteocalcin with the onset of mineralization, and 2) increases in AP and OP when DNA synthesis is inhibited. By determining cellular mRNA levels and rates of mRNA synthesis in isolated nuclei, we found that the down-regulation of cell growth-related genes is modified at both the levels of transcription and mRNA stability. For a histone gene where down-regulation is transcriptionally mediated, we have observed that the shutdown of osteoblast proliferation is associated with the selective loss of the interaction of a promoter binding factor (HiNF-D) with a proximal regulatory element (Site II). A relationship between Site II occupancy by HiNF-D and the onset of osteoblast differentiation is supported by the persistence of Site II-HiNF-D interactions when proliferating rat osteoblasts are growth arrested under conditions that do not induce differentiation; and additionally, by the loss of Site II-HiNF-D interactions during the shut-down of proliferation when HL60 promyelocytic leukemia cells are induced to differentiate into monocytes. Our results are consistent with a requirement of proliferation for expression of genes involved with production, deposition and possibly organization of the osteoblast extracellular matrix. It is also reasonable to postulate that properties of the mineralizing matrix are related to the shut-down of proliferation.</p>
dc.identifier.submissionpathstein/131
dc.contributor.departmentDepartment of Orthopedic Surgery
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages3-13


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