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dc.contributor.authorGalindo, Mario
dc.contributor.authorKahler, Rachel A.
dc.contributor.authorTeplyuk, Nadiya M.
dc.contributor.authorStein, Janet L.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.contributor.authorWestendorf, Jennifer J.
dc.contributor.authorVan Wijnen, Andre J.
dc.date2022-08-11T08:10:57.000
dc.date.accessioned2022-08-23T17:26:22Z
dc.date.available2022-08-23T17:26:22Z
dc.date.issued2007-09-22
dc.date.submitted2011-01-11
dc.identifier.citationJ Mol Histol. 2007 Oct;38(5):501-6. Epub 2007 Sep 21. <a href="http://dx.doi.org/10.1007/s10735-007-9143-0">Link to article on publisher's site</a>
dc.identifier.issn1567-2379 (Linking)
dc.identifier.doi10.1007/s10735-007-9143-0
dc.identifier.pmid17885813
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49622
dc.description.abstractRunt-related transcription factor Runx2 regulates osteogenic phenotype commitment and attenuates osteoblast growth. Runx2 levels are cell cycle regulated and maximal in the G1 phase of proliferating osteoblasts and during quiescence. The Wnt/Lrp5-Frizzled/beta-catenin/Lef-Tcf signaling cascade also controls progression along the osteogenic lineage with a net anabolic effect that promotes bone formation. However, Lef1 opposes the osteoblast maturation promoting activity of Runx2. Here we examined whether Lef1 controls Runx2 expression during the cell cycle or onset of quiescence in osteoblasts. We inhibited Lef1 expression using short hairpin (sh) RNA interference in stably transfected MC3T3-E1 cells. In asynchronously growing osteoblasts, expression of Lef1 shRNA diminishes Lef1 protein levels, but does not affect Runx2 levels. Cells arrested in different cell cycle stages using mimosine (late G1), hydroxyurea or aphidicolin (S phase) or nocodazole (mitosis) exhibit expected reductions in Runx2 protein levels despite reductions in Lef1. Serum deprived MC3T3-E1 cells normally upregulate Runx2 protein regardless of Lef1 deficiency, although loss of Lef1 reduces cyclin A and increases cyclin D1 expression upon serum withdrawal. Thus, Runx2 protein levels during the cell cycle and onset of quiescence are regulated independently of Lef1, one of the major transcriptional inducers of Wnt signaling in proliferating cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17885813&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1007/s10735-007-9143-0
dc.subject3T3 Cells
dc.subjectAnimals
dc.subjectAphidicolin
dc.subjectBlotting, Western
dc.subjectCell Cycle
dc.subjectCell Proliferation
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectHydroxyurea
dc.subjectLymphoid Enhancer-Binding Factor 1
dc.subjectMice
dc.subjectMimosine
dc.subjectNocodazole
dc.subjectOsteoblasts
dc.subjectRNA Interference
dc.subjectSignal Transduction
dc.subjectCell Biology
dc.titleCell cycle related modulations in Runx2 protein levels are independent of lymphocyte enhancer-binding factor 1 (Lef1) in proliferating osteoblasts
dc.typeArticle
dc.source.journaltitleJournal of molecular histology
dc.source.volume38
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/50
dc.identifier.contextkey1724090
html.description.abstract<p>Runt-related transcription factor Runx2 regulates osteogenic phenotype commitment and attenuates osteoblast growth. Runx2 levels are cell cycle regulated and maximal in the G1 phase of proliferating osteoblasts and during quiescence. The Wnt/Lrp5-Frizzled/beta-catenin/Lef-Tcf signaling cascade also controls progression along the osteogenic lineage with a net anabolic effect that promotes bone formation. However, Lef1 opposes the osteoblast maturation promoting activity of Runx2. Here we examined whether Lef1 controls Runx2 expression during the cell cycle or onset of quiescence in osteoblasts. We inhibited Lef1 expression using short hairpin (sh) RNA interference in stably transfected MC3T3-E1 cells. In asynchronously growing osteoblasts, expression of Lef1 shRNA diminishes Lef1 protein levels, but does not affect Runx2 levels. Cells arrested in different cell cycle stages using mimosine (late G1), hydroxyurea or aphidicolin (S phase) or nocodazole (mitosis) exhibit expected reductions in Runx2 protein levels despite reductions in Lef1. Serum deprived MC3T3-E1 cells normally upregulate Runx2 protein regardless of Lef1 deficiency, although loss of Lef1 reduces cyclin A and increases cyclin D1 expression upon serum withdrawal. Thus, Runx2 protein levels during the cell cycle and onset of quiescence are regulated independently of Lef1, one of the major transcriptional inducers of Wnt signaling in proliferating cells.</p>
dc.identifier.submissionpathstein/50
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages501-6


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