The Effect Of RhBMP-2 On VEGF Expression And Bone Healing For Treatment Of Bone Defect With Late-stage Osteotylus

IntroductionFracture nonunion is among common complications after orthopaedic surgery. Bone transplantation is widely accepted as an useful treatment, and autologous bone is viewed as the best transplant material. However, autograft still has its own complications.BMPs are members of the TGF-βsuperfamily. To date, researchers around the world has isolated more 20 members of BMP family with differing ability in bone induction. Among those, BMP-2 is considered to be most effective. Fracture repair is a complex pathological process, involving in proliferation and differentiation of various cells, together with anabolism and mineralization of extracellular matix, whose mechanism is still not fully understood. With the development of molecular cell biology, many cytokines at the frature site were found and their functions were investigated. Angiogenesis plays the central role in fracture repair, and is closely related with multiple factors such as FGF, TGF-α, TGF-β, PDGF,PGE,VEGF and TNF, etc. VEGF is extremely important, for it acts specifically with enthelial cells, contributing to cell proliferation, angiogenesis, and high vessel permeability. Questions were raised when we saw aboundance of osteotylus formed around the frature site in patients with chronic nonunion: can these osteotylus be used in combination with rhBMP-2 to replace the role of autologous iliac crest?In this study, we measured the expression of VEGF mRNA in animals models, comparing its activity, to further investigate and clarify the role of VEGF and angiogenesis in the process of fracture repair.AIMTo observe the effect on treating nonunion of late-stage callus around fracture site used in combination with recombinant human bone morphogenetic protein 2 (rhBMP-2), investigating the expression of vascular endothelial growth factor (VEGF) in callus and its influence on fracture healing.METHODSBilateral radial fractures were created in twenty Japanese rabbits. At 12 weeks after previous operation, all animals showed obvious osteotylus forming at the fratured site. The rabbits were randomly assigned for group I(10) and group II(10). Osteotylus were excised and a 1.5cm bone defect was created. In group I,the transplantation of rhBMP-2 and osteotylus was operated in left radius as group A, and transplantation of ilium in right radius was operated as group B. In group II, the transplantation of osteotylus in left radius was operated as group C, and blank control of right radius was set for group D. After 14 days of transplantation, all animals were killed and the expression of VEGF in different groups were investigated by means of reverse transcrip polymerase chain reaction (RT-PCR).RESULTSIn group A and B, there were no significant differences in protein and gene expression of VEGF. However, there were no obvious expression of VEGF in C,D group.CONCLUSIONTransplanting osteotylus around fracture site with recombinant rhBMP-2 accelerates the secretion of VEGF and fracture healing.