Abstract

The aim of this study was to explore the effect of adenosine A2A receptor agonists on fracture healing and the regulation of the immunity system after bone fracture. We implanted fibrin gel containing adenosine A2A receptor agonist CGS 21680/inhibitor ZM 241385/saline locally in rat tibial fracture models, finding that the adenosine A2A receptor agonist could promote fracture healing. At the same time, the adenosine A2A receptor agonist decreased the level of IL-6 in blood and the fracture area, increased Treg cells, and decreased Th17 cells in blood of bone fracture rats. Further, tibial fracture rats implanted with the adenosine A2A receptor agonist gel were injected with IL-6. We found that IL-6 could reverse the effect of adenosine A2A receptor agonists on fracture healing and Treg/Th17 cells in blood. Through the above results, we believe that the adenosine A2A receptor agonist can promote fracture healing and regulate Treg/Th17 cells in blood of rats with fractures. These effects are related to IL-6.

Highlights

  • How to promote bone healing and reduce the rate of nonunion is a hot topic within long-term research [1, 2]

  • There was no significant difference in the callus volume and bone mineralized tissue volume between the antagonist group and the control group at 1, 2, 4, 6, and 8 weeks (Figures 2–4)

  • It was found that adenosine A2A receptor agonists could reduce the level of IL-6 in the serum and local fracture tissues of rats at 1, 2, and 4 weeks, and the difference was statistically significant

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Summary

Introduction

How to promote bone healing and reduce the rate of nonunion is a hot topic within long-term research [1, 2]. Tibial shaft fractures are the most common long bone fracture and are prone to complications such as nonunion [6]. The incidence of complications in tibial shaft fractures, such as delayed union or nonunion, is 4–48% [7,8,9]. Surgical intervention and autologous bone transplantation are the gold standard of current treatment in the event of fracture nonunion, but the trauma is so large that some patients may need multiple surgeries for years [13,14,15]. Studies have found that allogeneic bone treatment for nonunion fractures takes about 12 months for allogeneic bone surface union; internal osteogenesis is very slow, occurring at a rate of only 15–20% within five years, and deep repair hardly occurs [13, 14]

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