Linked Life Data

11877389

Source:http://linkedlifedata.com/resource/pubmed/id/11877389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2002-5-13
pubmed:abstractText
Differentiating osteoblasts in culture undergo a commitment stage, during which cobblestone-like cells grow to high density past confluency. In contrast to earlier proliferative stages, the cell cycle during this commitment stage is inhibited by glucocorticoids (GC). Chronic GC treatment also impedes mineral deposition if steroid administration commences early enough during commitment. This study defines a role for glycogen synthase kinase-3beta (GSK3beta) and its target, c-Myc, in the GC-sensitive osteoblast persistent cell cycle. c-Myc levels decreased as cells reached confluence, but then increased during growth to high density. GC administration at this stage resulted in down-regulation of c-Myc. This was accompanied by GC-mediated attenuation of GSK3beta Ser(9) inhibitory phosphorylation and increased GSK3beta kinase activity. Down-regulation of c-Myc was attributable to enhanced Thr(58) phosphorylation, leading to accelerated degradation. In contrast, GC did not inhibit the c-Myc synthesis rate or the level of beta-catenin, a transcriptional coactivator of c-myc. The attenuated cell cycle and the reduced c-Myc level were returned to control levels by specific inhibition of GSK3beta using lithium chloride. These results suggest that tonal GSK3beta repression at the cobblestone stage of osteoblast differentiation permits osteoblast growth to high density. GC interfere with this growth-permissive axis by GSK3beta activation, resulting in c-Myc down-regulation and impediment of the G(1)/S cell cycle transition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18191-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11877389-Animals, pubmed-meshheading:11877389-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:11877389-Cell Cycle, pubmed-meshheading:11877389-Cell Differentiation, pubmed-meshheading:11877389-Cytoskeletal Proteins, pubmed-meshheading:11877389-Dimerization, pubmed-meshheading:11877389-Flow Cytometry, pubmed-meshheading:11877389-Glucocorticoids, pubmed-meshheading:11877389-Glycogen Synthase Kinase 3, pubmed-meshheading:11877389-Glycogen Synthase Kinases, pubmed-meshheading:11877389-Lithium, pubmed-meshheading:11877389-Osteoblasts, pubmed-meshheading:11877389-Phosphorylation, pubmed-meshheading:11877389-Proto-Oncogene Proteins c-myc, pubmed-meshheading:11877389-Serine, pubmed-meshheading:11877389-Trans-Activators, pubmed-meshheading:11877389-Up-Regulation, pubmed-meshheading:11877389-beta Catenin
pubmed:year
2002
pubmed:articleTitle
Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta.
pubmed:affiliation
Department of Orthopedic Surgery, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't