Abstract |
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.
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Authors | Shoko Onodera, Akiko Saito, Hironori Hojo, Takashi Nakamura, Denise Zujur, Katsuhito Watanabe, Nana Morita, Daigo Hasegawa, Hideki Masaki, Hiromitsu Nakauchi, Takeshi Nomura, Takahiko Shibahara, Akira Yamaguchi, Ung-Il Chung, Toshifumi Azuma, Shinsuke Ohba |
Journal | Stem cell reports
(Stem Cell Reports)
Vol. 15
Issue 1
Pg. 125-139
(07 14 2020)
ISSN: 2213-6711 [Electronic] United States |
PMID | 32531191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Chromogranins
- Hedgehog Proteins
- Transcription Factors
- GNAS protein, human
- GTP-Binding Protein alpha Subunits, Gs
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Topics |
- Basal Cell Nevus Syndrome
(pathology)
- Cell Culture Techniques
- Chromogranins
(genetics)
- GTP-Binding Protein alpha Subunits, Gs
(genetics)
- Gene Expression Profiling
- Hedgehog Proteins
(metabolism)
- Humans
- Induced Pluripotent Stem Cells
(cytology, metabolism)
- Mutation
(genetics)
- Osteoblasts
(metabolism)
- Osteogenesis
- Signal Transduction
- Transcription Factors
(metabolism)
- Transcriptome
(genetics)
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