Vascular Endothelial Growth Factor and Osteogenic-Angiogenic Coupling

This chapter focuses on vascular endothelial growth factor (VEGF) bone biology. It highlights the roles and regulation of VEGF receptor signaling during bone development, osteogenic–angiogenic coupling, matrix remodeling, fracture repair, and skeletal mineral metabolism. Bone never forms without vascular interactions. The vasculature provides the conduit for calcium, phosphate, hematopoietic, hormonal, and nutrient flux necessary for matrix synthesis, mineralization, and calcium mobilization. It provides the organizational structure and rate-limiting “point-of-reference” for Haversian bone formation, remodeling, and repair. Moreover, the vasculature provides a sustentacular niche and source of adult mesenchymal stem cells, including osteoprogenitors. During fracture repair, paracrine endothelial-mesenchymal signaling interactions are activated, recapitulating features of the epithelial-mesenchymal interactions that drive bone morphogenesis during embryonic development. Recent evidence suggests that circulating, marrow-derived endothelial progenitor cells (EPCs) may be delivered by the vasculature to sites of bone formation, and contribute not only to mature endothelial populations, but also to microvascular smooth muscle cells and osteoblast lineages during skeletal growth and fracture repair. In conclusion, VEGFA has emerged as the prototypic osteogenic-angiogenic coupling factor for bone-vascular interactions.