Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119886

Increased calvaria cell differentiation and bone matrix formation induced by fibroblast growth factor receptor 2 mutations in Apert syndrome.

A Lomri, J Lemonnier, M Hott, N de Parseval, E Lajeunie, A Munnich, D Renier, and P J Marie

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Lomri, A. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Lemonnier, J. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Hott, M. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by de Parseval, N. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Lajeunie, E. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Munnich, A. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Renier, D. in: JCI | PubMed | Google Scholar

INSERM U 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisière Hospital, 75475 Paris Cedex 10, France.

Find articles by Marie, P. in: JCI | PubMed | Google Scholar

Published March 15, 1998 - More info

Published in Volume 101, Issue 6 on March 15, 1998
J Clin Invest. 1998;101(6):1310–1317. https://doi.org/10.1172/JCI119886.
© 1998 The American Society for Clinical Investigation
Published March 15, 1998 - Version history
View PDF
Abstract

Apert syndrome, associated with fibroblast growth factor receptor (FGFR) 2 mutations, is characterized by premature fusion of cranial sutures. We analyzed proliferation and differentiation of calvaria cells derived from Apert infants and fetuses with FGFR-2 mutations. Histological analysis revealed premature ossification, increased extent of subperiosteal bone formation, and alkaline phosphatase- positive preosteoblastic cells in Apert fetal calvaria compared with age-matched controls. Preosteoblastic calvaria cells isolated from Apert infants and fetuses showed normal cell growth in basal conditions or in response to exogenous FGF-2. In contrast, the number of alkaline phosphatase- positive calvaria cells was fourfold higher than normal in mutant fetal calvaria cells with the most frequent Apert FGFR-2 mutation (Ser252Trp), suggesting increased maturation rate of cells in the osteoblastic lineage. Biochemical and Northern blot analyses also showed that the expression of alkaline phosphatase and type 1 collagen were 2-10-fold greater than normal in mutant fetal calvaria cells. The in vitro production of mineralized matrix formed by immortalized mutant fetal calvaria cells cultured in aggregates was also increased markedly compared with control immortalized fetal calvaria cells. The results show that Apert FGFR-2 mutations lead to an increase in the number of precursor cells that enter the osteogenic pathway, leading ultimately to increased subperiosteal bone matrix formation and premature calvaria ossification during fetal development, which establishes a connection between the altered genotype and cellular phenotype in Apert syndromic craniosynostosis.

Version history
  • Version 1 (March 15, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts