HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Hedgehog Activation Regulates Human Osteoblastogenesis.

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.
AuthorsShoko 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
JournalStem cell reports (Stem Cell Reports) Vol. 15 Issue 1 Pg. 125-139 (07 14 2020) ISSN: 2213-6711 [Electronic] United States
PMID32531191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: