Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair
Christa Maes, … , Roger Bouillon, Geert Carmeliet
Christa Maes, … , Roger Bouillon, Geert Carmeliet
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1230-1242. https://doi.org/10.1172/JCI26772.
View: Text | PDF
Research Article Bone biology Article has an altmetric score of 1

Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair

  • Text
  • PDF
Abstract

Current therapies for delayed- or nonunion bone fractures are still largely ineffective. Previous studies indicated that the VEGF homolog placental growth factor (PlGF) has a more significant role in disease than in health. Therefore we investigated the role of PlGF in a model of semistabilized bone fracture healing. Fracture repair in mice lacking PlGF was impaired and characterized by a massive accumulation of cartilage in the callus, reminiscent of delayed- or nonunion fractures. PlGF was required for the early recruitment of inflammatory cells and the vascularization of the fracture wound. Interestingly, however, PlGF also played a role in the subsequent stages of the repair process. Indeed in vivo and in vitro findings indicated that PlGF induced the proliferation and osteogenic differentiation of mesenchymal progenitors and stimulated cartilage turnover by particular MMPs. Later in the process, PlGF was required for the remodeling of the newly formed bone by stimulating osteoclast differentiation. As PlGF expression was increased throughout the process of bone repair and all the important cell types involved expressed its receptor VEGFR-1, the present data suggest that PlGF is required for mediating and coordinating the key aspects of fracture repair. Therefore PlGF may potentially offer therapeutic advantages for fracture repair.

Authors

Christa Maes, Lieve Coenegrachts, Ingrid Stockmans, Evis Daci, Aernout Luttun, Anna Petryk, Rajaram Gopalakrishnan, Karen Moermans, Nico Smets, Catherine M. Verfaillie, Peter Carmeliet, Roger Bouillon, Geert Carmeliet

×

Figure 10

Impaired bone remodeling in the absence of PlGF.

Options: View larger image (or click on image) Download as PowerPoint
Impaired bone remodeling in the absence of PlGF.
(A) Fracture callus dem...
(A) Fracture callus demonstrating the area shown in panels below (boxed region). Magnified views of WT and PlGF–/– calluses at PFW3 stained by safranin O. Red-stained cartilage proteoglycans were barely detectable within the woven bone in WT but abundant in PlGF–/– calluses. Also, woven bone in PlGF–/– mice was poorly surrounded by BM. (B) Sirius red staining at PFW3 showed that trabecular structures in PlGF–/– calluses were more robust and irregular than those in WT calluses. (C) 3D analysis of μCT scans of fractured tibias at PFW8 (n = 8–10). (D) Quantification of callus size at PFWs 4 and 6 based on digital X-rays. (E) TRAP staining of calluses at PFW3 showed smaller TRAP-positive cells in PlGF–/– mice versus WT. Bottom panels show magnified views. (F) Representative images of in vitro osteoclast formation using cultures of BM osteoclast progenitor cells treated with M-CSF and RANKL, showing impaired formation of large, multinuclear TRAP-positive cells in PlGF–/–-derived cultures compared with WT. (G) Quantification of in vitro osteoclast formation assays, confirming the reduced number of osteoclasts defined as TRAP-positive cells containing 3 or more nuclei (top), the increased proportion of mono- and dinuclear TRAP-positive cells (middle), and the decreased number of osteoclasts with large number of nuclei (bottom) in PlGF–/– cultures compared with WT (**P < 0.01, ***P < 0.001; 2-sided 2-sample Student’s t test). Scale bars: 150 μm (A and B), 50 μm (E, top panels), 25 μm (E, bottom panels), 500 μm (F).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Highlighted by 1 platforms
162 readers on Mendeley
See more details