Whole body application of nerve growth factor promotes early healing of tibial shaft fracture and improves expression of bone morphogenetic protein-2 and vascular endothelial growth factor in rats

doi:10.3969/j.issn.2095-4344.2780

Abstract

Abstract:

BACKGROUND: Fracture healing is a very complex, multi-stage physiological process with the coordinated participation of multiple cells. The influence of neurological factors on fracture healing has attracted increasing attention. Nerve growth factor is a bioactive complex protein that promotes cell growth. The mechanism of its role in promoting fracture healing is not clear.

OBJECTIVE: To observe the effect of nerve growth factor on the healing of tibial fracture in rats and the mechanism.

METHODS: Seventy-two male Sprague-Dawley rats were randomly divided into model group and treatment group. The model of tibial shaft closed fracture was established followed by intramedullary fixation. The treatment group was given intramuscular injection of nerve growth factor; the model group was given intramuscular injection of normal saline. The study was approved by the Experimental Animal Ethics Committee of Fujian Medical University on May 30, 2018, with approval No. FJYKDX-2018-035.

RESULTS AND CONCLUSION: The callus volume in the treatment group was significantly higher than that in the model group at 2 and 4 weeks of intervention. At 6 weeks of intervention, the fracture line disappeared, the medullary cavity was recanalized, and the fracture in the treatment group healed earlier than that in the control group. Hematoxylin-eosin staining showed that the trabeculae grew densely and a large number of osteoblasts were observed in the treatment group at 2 and 4 weeks after intervention. The serum alkaline phosphatase level in the treatment group was significantly higher than that in the model group at 2 and 4 weeks of intervention. Immunohistochemical results showed that the positive expression of bone morphogenetic protein 2 and vascular endothelial growth factor in the callus of treatment group was significantly higher than that of model group at 2 and 4 weeks after intervention. The results of quantitative PCR showed that the mRNA expression of bone morphogenetic protein 2 and vascular endothelial growth factor in the treatment group was higher than that in the model group at 2 and 4 weeks after intervention. To conclude, the whole body application of nerve growth factor can enhance the osteogenesis of tibial fracture end and promote the early healing of tibial fracture in rats. At the same time, nerve growth factor can promote the expression of bone morphogenetic protein 2 and vascular endothelial growth factor, which shows certain regularity in different periods, and in turn induces the differentiation and proliferation of osteoblasts as well as formation and calcification of extracellular matrix to promote bone formation and bone healing.

Key words: fracture healing, nerve growth factor, bone morphogenetic protein-2, vascular endothelial growth factor, tissue engineering, tibial fracture, osteoblasts, extracellular matrix

CLC Number:

Liu Guoming, Wang Qinfen, Lin Kefeng, Zhou Shiguo, Chen Zuxing, Lin Shishui. Whole body application of nerve growth factor promotes early healing of tibial shaft fracture and improves expression of bone morphogenetic protein-2 and vascular endothelial growth factor in rats[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(29): 4680-4685.

Figures/Tables 8

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