The role of vascular endothelial growth factor in ossification

Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator during these processes. It not only functions in bone angiogenesis but also in various aspects of bone development. Vascular endothelial growth factor (VEGF) plays roles in both blood vessel formation (angiogenesis) and bone formation (osteogenesis). Scientists knew that VEGF is a trigger for vascularization. However, a growing body of work suggests that it also modulates the behavior of cells that form and remodel bone. After reviewing the literature, a team led by Yan-Qi Yang of the University of Hong Kong, China, compiled the evidence supporting this dual role for VEGF. Long bones such as limbs are formed by a mechanism called ‘endochondral ossification’, and numerous studies suggest that VEGF regulates this process directly and indirectly through its angiogenic effects. Other bones, like those in the face, form from connective tissue via ‘intramembranous ossification’. VEGF similarly helps to coordinate migration and differentiation of bone cells during this process.