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 ...
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • 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
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP
Tatsuya Kobayashi, … , Andrew P. McMahon, Henry M. Kronenberg
Tatsuya Kobayashi, … , Andrew P. McMahon, Henry M. Kronenberg
Published July 1, 2005
Citation Information: J Clin Invest. 2005;115(7):1734-1742. https://doi.org/10.1172/JCI24397.
View: Text | PDF
Research Article Bone Biology

Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP

  • Text
  • PDF
Abstract

In the developing growth plate, periarticular chondrocytes proliferate, differentiate into columnar chondrocytes, and then further differentiate into postmitotic hypertrophic chondrocytes. Parathyroid hormone–related (PTH-related) protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, thereby maintaining the length of columns. Ihh regulates cartilage development through PTHrP-independent pathways as well. Here we show that Ihh stimulates differentiation of periarticular to columnar chondrocytes (periarticular chondrocyte differentiation) and thereby regulates the length of columns independently of PTHrP. Mosaic ablation of the PTH/PTHrP receptor in the growth plate caused upregulation of Ihh action, PTHrP upregulation, acceleration of periarticular chondrocyte differentiation, and elongation of the columnar region. Decreasing Ihh action in these mice reduced elongation of columns, whereas decreasing PTHrP showed only a modest effect on column length. Overexpression of Ihh caused PTHrP upregulation, elongation of columns, and acceleration of periarticular chondrocyte differentiation. PTHrP heterozygosity in this model had a minimal effect on the elongation of columns. Moreover, the elongation of columns and stimulation of periarticular chondrocyte differentiation in these models were still observed when PTHrP signaling was maintained so that it remained constant. These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP.

Authors

Tatsuya Kobayashi, Desi W. Soegiarto, Yingzi Yang, Beate Lanske, Ernestina Schipani, Andrew P. McMahon, Henry M. Kronenberg

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Effect of PTHrP heterozygosity on the length of the growth plate. Alcian...
Effect of PTHrP heterozygosity on the length of the growth plate. Alcian blue–stained growth plates of E17.5 proximal tibiae from wild-type and E16.5 proximal tibiae from Ost-Cre:PPRfl/– mice (A) and E16.5 distal tibiae from control (Col2-GAL4) and Col2-GAL4:UAS-cIhh (Ihh-Bg) mice (B) in PPR+/+ and PPR+/– backgrounds are shown. In situ hybridization confirmed a reduction in PTHrP expression in Ihh-Bg:PTHrP+/– mice. Littermates were compared. Growth plates of PPR+/– mice were shorter than those of controls by approximately 8% regardless of other genetic modifications.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts