title: Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair.
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.
authors.affiliation: Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Christa
authors.initials: C
authors.lastname: Maes
authors.forename: Lieve
authors.initials: L
authors.lastname: Coenegrachts
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stockmans
authors.forename: Evis
authors.initials: E
authors.lastname: Daci
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
authors.forename: Rajaram
authors.initials: R
authors.lastname: Gopalakrishnan
authors.forename: Karen
authors.initials: K
authors.lastname: Moermans
authors.forename: Nico
authors.initials: N
authors.lastname: Smets
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
mesh_terms: 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
chemical_list: C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1