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Hedgehog Activation Regulates Human Osteoblastogenesis
Two genetic diseases, Gorlin syndrome and McCune-Albright syndrome (MAS), show completely opposite symptoms in terms of bone mineral density and hedgehog (Hh) activity. In this study, we utilized human induced pluripotent stem cell (iPSC)-based models of the two diseases to understand the roles of H...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363748/ https://www.ncbi.nlm.nih.gov/pubmed/32531191 http://dx.doi.org/10.1016/j.stemcr.2020.05.008 |
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author | Onodera, Shoko Saito, Akiko Hojo, Hironori Nakamura, Takashi Zujur, Denise Watanabe, Katsuhito Morita, Nana Hasegawa, Daigo Masaki, Hideki Nakauchi, Hiromitsu Nomura, Takeshi Shibahara, Takahiko Yamaguchi, Akira Chung, Ung-il Azuma, Toshifumi Ohba, Shinsuke |
author_facet | Onodera, Shoko Saito, Akiko Hojo, Hironori Nakamura, Takashi Zujur, Denise Watanabe, Katsuhito Morita, Nana Hasegawa, Daigo Masaki, Hideki Nakauchi, Hiromitsu Nomura, Takeshi Shibahara, Takahiko Yamaguchi, Akira Chung, Ung-il Azuma, Toshifumi Ohba, Shinsuke |
author_sort | Onodera, Shoko |
collection | PubMed |
description | Two genetic diseases, Gorlin syndrome and McCune-Albright syndrome (MAS), show completely opposite symptoms in terms of bone mineral density and hedgehog (Hh) activity. In this study, we utilized human induced pluripotent stem cell (iPSC)-based models of the two diseases to understand the roles of Hh signaling in osteogenesis. Gorlin syndrome-derived iPSCs showed increased osteoblastogenesis and mineralization with Hh signaling activation and upregulation of a set of transcription factors in an osteogenic culture, compared with the isogenic control. MAS-specific iPSCs showed poor mineralization with low Hh signaling activity in the osteogenic culture; impaired osteoblastogenesis was restored to the normal level by treatment with an Hh signaling-activating small molecule. These data suggest that Hh signaling is a key controller for differentiation of osteoblasts from precursors. This study may pave a path to new drug therapies for genetic abnormalities in calcification caused by dysregulation of Hh signaling. |
format | Online Article Text |
id | pubmed-7363748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73637482020-07-20 Hedgehog Activation Regulates Human Osteoblastogenesis Onodera, Shoko Saito, Akiko Hojo, Hironori Nakamura, Takashi Zujur, Denise Watanabe, Katsuhito Morita, Nana Hasegawa, Daigo Masaki, Hideki Nakauchi, Hiromitsu Nomura, Takeshi Shibahara, Takahiko Yamaguchi, Akira Chung, Ung-il Azuma, Toshifumi Ohba, Shinsuke Stem Cell Reports Article Two genetic diseases, Gorlin syndrome and McCune-Albright syndrome (MAS), show completely opposite symptoms in terms of bone mineral density and hedgehog (Hh) activity. In this study, we utilized human induced pluripotent stem cell (iPSC)-based models of the two diseases to understand the roles of Hh signaling in osteogenesis. Gorlin syndrome-derived iPSCs showed increased osteoblastogenesis and mineralization with Hh signaling activation and upregulation of a set of transcription factors in an osteogenic culture, compared with the isogenic control. MAS-specific iPSCs showed poor mineralization with low Hh signaling activity in the osteogenic culture; impaired osteoblastogenesis was restored to the normal level by treatment with an Hh signaling-activating small molecule. These data suggest that Hh signaling is a key controller for differentiation of osteoblasts from precursors. This study may pave a path to new drug therapies for genetic abnormalities in calcification caused by dysregulation of Hh signaling. Elsevier 2020-06-11 /pmc/articles/PMC7363748/ /pubmed/32531191 http://dx.doi.org/10.1016/j.stemcr.2020.05.008 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Onodera, Shoko Saito, Akiko Hojo, Hironori Nakamura, Takashi Zujur, Denise Watanabe, Katsuhito Morita, Nana Hasegawa, Daigo Masaki, Hideki Nakauchi, Hiromitsu Nomura, Takeshi Shibahara, Takahiko Yamaguchi, Akira Chung, Ung-il Azuma, Toshifumi Ohba, Shinsuke Hedgehog Activation Regulates Human Osteoblastogenesis |
title | Hedgehog Activation Regulates Human Osteoblastogenesis |
title_full | Hedgehog Activation Regulates Human Osteoblastogenesis |
title_fullStr | Hedgehog Activation Regulates Human Osteoblastogenesis |
title_full_unstemmed | Hedgehog Activation Regulates Human Osteoblastogenesis |
title_short | Hedgehog Activation Regulates Human Osteoblastogenesis |
title_sort | hedgehog activation regulates human osteoblastogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363748/ https://www.ncbi.nlm.nih.gov/pubmed/32531191 http://dx.doi.org/10.1016/j.stemcr.2020.05.008 |
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