Hedgehog Activation Regulates Human Osteoblastogenesis.

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 Mutation / genetics Osteoblasts / metabolism Osteogenesis Signal Transduction Transcription Factors / metabolism Transcriptome / genetics
Gorlin syndrome McCune-Albright syndrome calcification fibrous dysplasia hedgehog pathway osteogenesis patient-specific iPSC

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
14 07 2020
Historique:
received: 23 01 2020
revised: 12 05 2020
accepted: 13 05 2020
pubmed: 13 6 2020
medline: 3 6 2021
entrez: 13 6 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.stemcr.2020.05.008 PMID: 32531191 PMC: PMC7363748
pubmed: 32531191
pii: S2213-6711(20)30180-6
doi: 10.1016/j.stemcr.2020.05.008
pmc: PMC7363748
pii:
doi:

Substances chimiques

Chromogranins 0
Hedgehog Proteins 0
Transcription Factors 0
GNAS protein, human EC 3.6.1.-
GTP-Binding Protein alpha Subunits, Gs EC 3.6.5.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

125-139

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Références

Dermatol Clin. 1995 Jan;13(1):113-25
pubmed: 7712637
Trends Cell Biol. 2002 Dec;12(12):562-9
pubmed: 12495844
Development. 2006 Aug;133(16):3231-44
pubmed: 16854976
Int J Mol Med. 2006 Jan;17(1):171-5
pubmed: 16328026
J Clin Invest. 2012 Oct;122(10):3490-503
pubmed: 22945629
Cell Metab. 2010 Feb 3;11(2):136-46
pubmed: 20142101
J Biol Chem. 2008 Apr 4;283(14):9224-30
pubmed: 18250171
Genes Dev. 2001 Dec 1;15(23):3059-87
pubmed: 11731473
Biochem Biophys Res Commun. 2007 Jun 15;357(4):854-60
pubmed: 17451649
J Bone Joint Surg Am. 2008 Feb;90 Suppl 1:19-24
pubmed: 18292352
Nat Med. 2013 Nov;19(11):1505-12
pubmed: 24076664
J Clin Invest. 2013 Aug;123(8):3409-19
pubmed: 23867625
Nat Rev Mol Cell Biol. 2013 Jul;14(7):416-29
pubmed: 23719536
Nat Rev Rheumatol. 2015 Sep;11(9):552-60
pubmed: 26077918
Sci Adv. 2017 May 12;3(5):e1602875
pubmed: 28508073
Science. 1997 Aug 22;277(5329):1109-13
pubmed: 9262482
Bone Res. 2018 Nov 20;6:33
pubmed: 30479847
Development. 2009 Dec;136(24):4177-85
pubmed: 19906844
Mol Cell Biol. 2010 Apr;30(8):1910-22
pubmed: 20154143
Nature. 2002 Aug 29;418(6901):979-83
pubmed: 12198547
Cell. 2000 Feb 18;100(4):423-34
pubmed: 10693759
Development. 2004 Mar;131(6):1309-18
pubmed: 14973297
J Biol Chem. 2010 Oct 1;285(40):31055-65
pubmed: 20650891
Dev Cell. 2008 May;14(5):689-99
pubmed: 18477452
J Biol Chem. 2006 Nov 24;281(47):35598-602
pubmed: 17035233
Development. 2008 Jan;135(2):237-47
pubmed: 18057099
Curr Osteoporos Rep. 2015 Jun;13(3):146-58
pubmed: 25851935
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E418-E427
pubmed: 29158412
PLoS One. 2017 Oct 31;12(10):e0186879
pubmed: 29088246
Cell Metab. 2010 Feb 3;11(2):147-60
pubmed: 20142102
N Engl J Med. 1991 Dec 12;325(24):1688-95
pubmed: 1944469
Stem Cell Reports. 2014 May 22;2(6):751-60
pubmed: 24936463
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1401-1408
pubmed: 30025894
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4726-30
pubmed: 1584809
J Cell Biol. 2002 Apr 15;157(2):303-14
pubmed: 11956231
Genes Dev. 1999 Aug 15;13(16):2072-86
pubmed: 10465785
Pediatr Int. 2014 Oct;56(5):667-74
pubmed: 25131638
Development. 1998 Dec;125(23):4767-76
pubmed: 9806925
Cell. 1997 May 30;89(5):755-64
pubmed: 9182763
N Engl J Med. 1960 May 5;262:908-12
pubmed: 13851319
Mol Endocrinol. 2004 May;18(5):1222-37
pubmed: 14976225
Dev Biol. 2007 May 15;305(2):460-9
pubmed: 17400206

Auteurs

Shoko Onodera (S)

Department of Biochemistry, Tokyo Dental College, Tokyo 101-0061, Japan; Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan.

Akiko Saito (A)

Department of Biochemistry, Tokyo Dental College, Tokyo 101-0061, Japan.

Hironori Hojo (H)

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8655, Japan.

Takashi Nakamura (T)

Department of Biochemistry, Tokyo Dental College, Tokyo 101-0061, Japan.

Denise Zujur (D)

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan.

Katsuhito Watanabe (K)

Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo 101-0061, Japan.

Nana Morita (N)

Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba 272-8513, Japan.

Daigo Hasegawa (D)

Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo 101-0061, Japan.

Hideki Masaki (H)

Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Hiromitsu Nakauchi (H)

Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305-5461, USA.

Takeshi Nomura (T)

Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba 272-8513, Japan.

Takahiko Shibahara (T)

Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo 101-0061, Japan.

Akira Yamaguchi (A)

Oral Health Science Center, Tokyo Dental College, Tokyo 101-0061, Japan.

Ung-Il Chung (UI)

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8655, Japan.

Toshifumi Azuma (T)

Department of Biochemistry, Tokyo Dental College, Tokyo 101-0061, Japan; Oral Health Science Center, Tokyo Dental College, Tokyo 101-0061, Japan. Electronic address: tazuma@tdc.ac.jp.

Shinsuke Ohba (S)

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8655, Japan; Department of Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan. Electronic address: s-ohba@nagasaki-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Syndromes néoplasiques héréditaires › Naevomatose basocellulaire › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Précurseurs de protéines › Chromogranine › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines G hétérotrimériques › Sous-unités alpha des protéines G › Sous-unités alpha Gs des protéines G › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Ostéoblastes › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Biominéralisation › Développement osseux › Ostéogenèse › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Hedgehog Activation Regulates Human Osteoblastogenesis.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Hedgehog Activation Regulates Human Osteoblastogenesis.