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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.
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Research Article Bone biology

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

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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

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Figure 5

PlGF affects the osteoblastic differentiation of MAPCs.

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PlGF affects the osteoblastic differentiation of MAPCs.
(A) Osteoblastic...
(A) Osteoblastic differentiation of mouse MAPCs cultured for 14 days in medium containing ascorbic acid (osteoblastic differentiation medium; D) compared with control medium (C). At days 2, 4, 7, and 14, the expression of the osteoblast markers Runx2, osterix, ALP, bone sialoprotein (BSP), and osteocalcin (OC) was evaluated by RT-PCR using GAPDH as a housekeeping gene. (B) Levels of expression of VEGFR-1 mRNA and osteocalcin in MAPCs during the course of osteoblastic differentiation measured by qRT-PCR. Values are expressed as GAPDH-corrected levels for MAPCs cultured in differentiation medium relative to control medium for the same period. The experiment was performed 3 times. *P < 0.05 versus day 0. (C) ALP activity was significantly increased after rPlGF treatment of MAPCs cultured in differentiation medium for 7 days. Results are expressed as percentage of ALP activity in differentiating cultures incubated with vehicle. (D) Phase-contrast microscopy of MAPC cultures showing the effect on mineralization of adding rPlGF to the medium. At day 21, MAPCs cultured in osteoblastic differentiation medium showed extensive mineralization compared with MAPCs cultured in control medium. Mineralization was enhanced by adding rPlGF to the differentiation medium. Graph shows the quantification of the mineralized area expressed as percentage of the surface examined, revealing a significant increase by rPlGF addition. **P < 0.01; ***P < 0.001.

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

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