External axial Stress Induces Rabbit Tibia Fracture Healing via Stimulating the Expression of VEGF, CD34, BMP-2 and TGF-β1

Abstract

BackgroundIt is well acknowledged that stress stimulation can promote the healing rate of fracture. However, there were few literature that described the relationship between stress stimulation at the fracture site and the molecular mechanism in fracture healing process. The aim of this study was to investigate whether external axial stress, provided by the stimulator, postoperatively, can accelerate the union of rabbit tibial fracture, and to reveal the possible mechanism.MethodsSeventy-two New Zealand rabbit tibial fracture models were established and randomly divided into two groups. Rabbits in experiment group (n=36) were subjected to external axial stress stimulation for 30 minutes every two days from the eighth day postoperative, but rabbits in control group received no stress stimulation. All rabbits were treated with external plaster for limb immobilization after operation. Lane-Sandhu X-ray evaluation system was used to evaluate the bone healing process at 2, 4, 6 and 8 weeks postoperative. Specimens were harvested for immunohistochemical test and semi quantitative analysis. They were applied to evaluate the expression of vascular endothelial growth factor (VEGF), CD34, bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) at postoperative2,4,6and8weeks,respectively.ResultsThe mean Lane-Sandhu X-ray score of experiment group was significantly higher than control group at 4, 6 and 8 weeks (P<0.05, P<0.01 and P<0.01，respectively). More callus and better calcification were observed in the experiment group. The expression of VEGF (P<0.01, P<0.05, P<0.01, P<0.01, respectively) and BMP-2 (P<0.05, P<0.05, P<0.01, P<0.01, respectively) at each phase in the experiment group was significantly higher than the control group. The expression of CD34 (P<0.01 and P<0.01, respectively) and TGF-β1(P<0.01, P<0.01, respectively) in experimental group was higher than control group at2and4weeks.ConclusionsPostoperative external axial stress stimulation can facilitate the expression of VEGF, CD34, BMP-2 and TGF-β1, and stimulate the vascularization and ossification of the fracture site, therefore,acceleratethefractureunion.