β-NGF Effect On Angiogenesis And Neurogenesis During Bone Healing Process

Objective:To investigate the effect of local application beta-NGF on nerve regeneration duringthe process of bone healing, and further test the hypothesis that neurogenesis mayaffect angiogenesis via increasing expression of VEGF/VEGFR-2.Methods:30male adult Sprague-Dawley(SD) rats were separated into5groups. Two5-mmdiameter critical bone defects were symmetrically created on the parietal bonefollowed by the placement of college I bone substitute into the bone defects. The bonedefect on the right side was given by10ug beta-NGF PBS solution and the left sidewas given only by PBS solution via osmotic pump over7days after surgery. Ratswere euthanized at3、7、14、21、and28days time points postsurgery. The pan-neuronal marker PGP9.5, the neurofilaments medium160(NF160), neuronaldifferentiation marker β III-tubulin, and angiogenesis promoter VEGF/VEGFR-2were studied by immunohistochemical staining. Furthermore, angiogenesis was alsoassessed by counting the number of blood vessels.Results:Significant increasing of NF160at7days time point, PGP9.5、β III-tubulin at14days time point were showed within the beta-NGF side compare with the PBS side bysemi-quantitative analysis of average optical density(AOD) revealed. The expressionof VEGF increased significant increasing AOD of VEGF at7days and theexpression of VEGFR-2increased at14、21days in the beta-NGF side. Even thoughthe number of blood vessels showed no significant difference between the beta-NGFside and the PBS side at each tiome point, the number of blood vessels in the beta-NGF side was almost1.5-fold to the PBS side at7days. At28days, the expression of PGP9.5、β III-tubulin andVEGFR-2significant decreased within the beta-NGFside compared to the PBS side.Conclusion:In conclusion, local application of β-NGF can promote neurogenesis during bonehealing, and the nerve regeneration can affect angiogenesis via the synthetize andexpression of VEGF/VEGFR-2. It is concluded that change of one system (bone,blood vessel, nerve system) will result in change of the other systems.