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Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice

Indian hedgehog (Ihh) signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation...

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Detalles Bibliográficos
Autores principales: Joeng, Kyu Sang, Long, Fanxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559391/
https://www.ncbi.nlm.nih.gov/pubmed/23383082
http://dx.doi.org/10.1371/journal.pone.0055134
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author Joeng, Kyu Sang
Long, Fanxin
author_facet Joeng, Kyu Sang
Long, Fanxin
author_sort Joeng, Kyu Sang
collection PubMed
description Indian hedgehog (Ihh) signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh) signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.
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spelling pubmed-35593912013-02-04 Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice Joeng, Kyu Sang Long, Fanxin PLoS One Research Article Indian hedgehog (Ihh) signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh) signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism. Public Library of Science 2013-01-30 /pmc/articles/PMC3559391/ /pubmed/23383082 http://dx.doi.org/10.1371/journal.pone.0055134 Text en © 2013 Joeng, Long 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
Joeng, Kyu Sang
Long, Fanxin
Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title_full Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title_fullStr Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title_full_unstemmed Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title_short Constitutive Activation of Gli2 Impairs Bone Formation in Postnatal Growing Mice
title_sort constitutive activation of gli2 impairs bone formation in postnatal growing mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559391/
https://www.ncbi.nlm.nih.gov/pubmed/23383082
http://dx.doi.org/10.1371/journal.pone.0055134
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