Angiogenic-osteogenic coupling: the role of the PDGF family in the crosstalk between osteoprogenitors and endothelial cells, and implications thereof in bone biology and repair

Osteoporosis-induced fractures pose an increasing medical and economic burden. There is a large interest in osteo-anabolic therapies that can restore the low bone mass in osteoporotic patients to reduce the fracture risk, or stimulate bone formation when healing is compromised. It is well known that the presence of blood vessels is absolutely required for bone formation, but our understanding of this coupling is incomplete. Intriguingly, neovascularization of developing and healing bones is associated with co-migration of osteoprogenitors (OPs), some being wrapped around the vessels as pericytes. This has led us to hypothesize that blood vessels may provide guiding cues for OP trafficking to sites of bone formation. Here, we propose that crosstalk between endothelial cells and OPs via the platelet-derived growth factor (PDGF) family may be important for the recruitment of osteogenic cells to blood vessels, and for steering OP migration towards bone formation sites. Using in vitro approaches and advanced animal models we will dissect the specific contributions of endothelial PDGF production and osteoblastic PDGF receptor signaling to bone growth, homeostasis and repair. This project will deliver a comprehensive understanding of how the PDGF family functions in angiogenic-osteogenic coupling, and identify the importance of this crosstalk in bone biology and repair. These basic and translational insights will contribute to the active exploration of PDGF-based fracture therapies.