The osteogenic-angiogenic interface: Novel insights into the biology of bone formation and fracture repair

Bone never forms without vascular interactions. Although this is a very simple and obvious statement, the biological, clinical, and pharmacologic implications are incompletely appreciated. The vasculature is not only the conduit for nutrient-metabolite exchange and the rate-limiting "point-of-reference" for Haversian bone formation, but also provides the sustentacular niche for the self-renewing osteoprogenitor. This past year, significant advances have been made in our understanding of the osteogenic-angiogenic interface that are immediately germane to osteoporosis disease biology and fracture management. The critical contributions of the osteoblast oxygen-sensing machinery, paracrine vascular endothelial growth factor and placental growth factor signaling, fracture-mobilized circulating osteoprogenitors, and the osteogenic CD146(+) marrow sinusoid stem cell have been recently discovered. This brief review recounts these revelations, highlighting the potential impact to human bone health and fracture repair.