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Title: Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair
Authors: Maes, Christa ×
Coenegrachts, Lieve
Stockmans, Ingrid
Daci, Evis
Luttun, Aernout
Petryk, Anna
Gopalakrishnan, Rajaram
Moermans, Karen
Smets, Nico
Verfaillie, Catherine
Carmeliet, Peter
Bouillon, Roger
Carmeliet, Geert #
Issue Date: May-2006
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:116 issue:5 pages:1230-1242
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 semi-stabilized 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.
URI: 
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Molecular and Vascular Biology
Interdepartemental Stem Cell Institute (-)
Gynaecological Oncology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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