VEGF and BMP4 interaction in bone formation

IntroductionAngiogenesis and bone formation are coupled during skeletal development and fracture healing. Advances in the discovery of how angiogenesis is regulated in physiological processes have provided a deeper understanding of how angiogenic factors may interact with bone cells to improve bone formation and bone regeneration.ObjectivesWe studied the interaction between VEGF and BMP4 during bone formation and bone healing.MethodsA thorough Medline database search performed on related MeSH terms yielded 100 titles and selected abstracts that were independently screened. Out of the 60 abstracts selected, 35 full-text articles were obtained for further evaluationResultsResults showed that although VEGF alone did not improve bone regeneration, it acted synergistically with BMP4 to increase recruitment of mesenchymal stem cells, to enhance cell survival, and to augment cartilage formation in the early stages of endochondral bone formation. These early effects, coupled with accelerated cartilage resorption, eventually led to a significant enhancement of bone formation and bone healing. The beneficial effect of VEGF on bone healing elicited by BMP4 depends on the ratio of VEGF to BMP4.ConclusionEGF activity is required for optimal bone formation elicited by MDSCs expressing BMP4. VEGF in the presence of BMP4 promotes recruitment of mesenchymal cells to bone formation and regeneration sites and enhances cell survival, subsequently leading to augmented cartilage formation. Thus, VEGF enhances BMP4-elicited endochondral bone formation not only by influencing steps after cartilage formation, but also by affecting steps in the early stages of the bone formation cascade.

کلیدواژه ها:

Bone morphogenetic protein ، Bone formation ، Vascular endothelial growth factor