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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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Autores principales: Kugimiya, Fumitaka, Kawaguchi, Hiroshi, Ohba, Shinsuke, Kawamura, Naohiro, Hirata, Makoto, Chikuda, Hirotaka, Azuma, Yoshiaki, Woodgett, James R., Nakamura, Kozo, Chung, Ung-il
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950686/
https://www.ncbi.nlm.nih.gov/pubmed/17786208
http://dx.doi.org/10.1371/journal.pone.0000837
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author Kugimiya, Fumitaka
Kawaguchi, Hiroshi
Ohba, Shinsuke
Kawamura, Naohiro
Hirata, Makoto
Chikuda, Hirotaka
Azuma, Yoshiaki
Woodgett, James R.
Nakamura, Kozo
Chung, Ung-il
author_facet Kugimiya, Fumitaka
Kawaguchi, Hiroshi
Ohba, Shinsuke
Kawamura, Naohiro
Hirata, Makoto
Chikuda, Hirotaka
Azuma, Yoshiaki
Woodgett, James R.
Nakamura, Kozo
Chung, Ung-il
author_sort Kugimiya, Fumitaka
collection PubMed
description 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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spelling pubmed-19506862007-09-05 GSK-3β Controls Osteogenesis through Regulating Runx2 Activity Kugimiya, Fumitaka Kawaguchi, Hiroshi Ohba, Shinsuke Kawamura, Naohiro Hirata, Makoto Chikuda, Hirotaka Azuma, Yoshiaki Woodgett, James R. Nakamura, Kozo Chung, Ung-il PLoS One Research Article 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. Public Library of Science 2007-09-05 /pmc/articles/PMC1950686/ /pubmed/17786208 http://dx.doi.org/10.1371/journal.pone.0000837 Text en Kugimiya et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kugimiya, Fumitaka
Kawaguchi, Hiroshi
Ohba, Shinsuke
Kawamura, Naohiro
Hirata, Makoto
Chikuda, Hirotaka
Azuma, Yoshiaki
Woodgett, James R.
Nakamura, Kozo
Chung, Ung-il
GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title_full GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title_fullStr GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title_full_unstemmed GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title_short GSK-3β Controls Osteogenesis through Regulating Runx2 Activity
title_sort gsk-3β controls osteogenesis through regulating runx2 activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950686/
https://www.ncbi.nlm.nih.gov/pubmed/17786208
http://dx.doi.org/10.1371/journal.pone.0000837
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