Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair.
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.
Maes
Christa
C
Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
Coenegrachts
Lieve
L
Stockmans
Ingrid
I
Daci
Evis
E
Luttun
Aernout
A
Petryk
Anna
A
Gopalakrishnan
Rajaram
R
Moermans
Karen
K
Smets
Nico
N
Verfaillie
Catherine M
CM
Carmeliet
Peter
P
Bouillon
Roger
R
Carmeliet
Geert
G
D000818:Animals; D016723:Bone Remodeling; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D017102:Fracture Healing; D007249:Inflammation; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1