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.
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
Title and authors | Publication | Year |
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Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis
L Lieben, BS Benn, D Ajibade, I Stockmans, K Moermans, MA Hediger, JB Peng, S Christakos, R Bouillon, G Carmeliet |
Bone | 2010 |
Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement
AP Taylor, E Leon, DM Goldenberg |
British Journal of Cancer | 2010 |
Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels
C Maes, T Kobayashi, MK Selig, S Torrekens, SI Roth, S Mackem, G Carmeliet, HM Kronenberg |
Developmental Cell | 2010 |
Production of VEGF receptor 1 and 2 mRNA and protein during endochondral bone repair is differential and healing phase specific
MK Reumann, T Nair, O Strachna, AL Boskey, P Mayer-Kuckuk |
Journal of applied physiology | 2010 |