| Description en | Osteoporosis and non-healing fractures pose an increasing clinical problem worldwide, echoing the need for new osteo-anabolic drugs and improved therapies for bone repair. Platelet-derived growth factor (PDGF) is widely considered for use in clinical orthopedics. A full understanding of the mechanisms of action of the PDGF ligands and receptors in bone homeostasis and fracture healing, as well as their effects within the bone marrow environment, is thus imperative and timely and of high clinical relevance.Preceding data obtained in our lab indicated that signaling via PDGFR in osteoprogenitors is important for bone repair in mice, by regulating osteo-angiogenic crosstalk and recruitment of PGDFR osteogenic cells. Interestingly, PDGFRs are increasingly recognized to mark subsets of (partly perivascular) mesenchymal progenitors in bone. The functional significance of signaling through these receptors has, however, not been analyzed in vivo.We will here assess the role of endothelial-derived PDGF in osteo-angiogenic coupling, and of skeletal progenitor cell-expressed PDGFRs in their activation and recruitment for bone formation, cell fate specification, and hematopoiesis support.This study will increase our knowledge on the roles of the PDGF family in bone, and on the communication between skeletal progenitors, blood vessels, and hematopoietic stem cells in their bone marrow niches, possibly leading to new osteo-anabolic therapies and bone tissue engineering applications.
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