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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3559391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT joengkyusang constitutiveactivationofgli2impairsboneformationinpostnatalgrowingmice AT longfanxin constitutiveactivationofgli2impairsboneformationinpostnatalgrowingmice |