GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
Despite accumulated knowledge of various signalings regulating bone formation, the molecular network has not been clarified sufficiently to lead to clinical application. Here we show that heterozygous glycogen synthase kinase-3β (GSK-3β)-deficient mice displayed an increased bone formation due to an...
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Published in | PloS one Vol. 2; no. 9; p. e837 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
San Francisco
Public Library of Science
05.09.2007
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Subjects | |
Online Access | Get full text |
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Summary: | Despite accumulated knowledge of various signalings regulating bone formation, the molecular network has not been clarified sufficiently to lead to clinical application. Here we show that heterozygous glycogen synthase kinase-3β (GSK-3β)-deficient mice displayed an increased bone formation due to an enhanced transcriptional activity of Runx2 by suppressing the inhibitory phosphorylation at a specific site. The cleidocranial dysplasia in heterozygous Runx2-deficient mice was significantly rescued by the genetic insufficiency of GSK-3β or the oral administration of lithium chloride, a selective inhibitor of GSK-3β. These results establish GSK-3β as a key attenuator of Runx2 activity in bone formation and as a potential molecular target for clinical treatment of bone catabolic disorders like cleidocranial dysplasia. |
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Bibliography: | Conceived and designed the experiments: HK FK UC. Performed the experiments: NK FK SO MH. Analyzed the data: FK KN. Contributed reagents/materials/analysis tools: JW NK SO HC YA. Wrote the paper: FK. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0000837 |