Abstract

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young’s modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.

Highlights

  • Long-bone fracture is a common musculoskeletal trauma representing a considerable burden of disease

  • Our results revealed that treatment with EGCG, at 10 μmol/L, significantly accelerated the fracture healing and improved the mechanical strength of the fractured tibia

  • EGCG could regulate the RANK ligand (RANKL)-induced osteoclastogenesis and possibly reduce the resorption of woven bones and increase the callus size, which may be another possible mechanism for increased tibia fracture healing

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Summary

Introduction

Long-bone fracture is a common musculoskeletal trauma representing a considerable burden of disease. Numerous clinical studies indicated a positive effect between tea consumption and bone health [2]. Those who drink tea habitually have better bone mineral density (BMD) and a lower hip fracture rate [3,4]. Numerous clinical and animal studies indicated that tea can increase bone volume and diminish osteoporotic fractures, the relationship between tea consumption and fracture healing remained unclear. We found that local treatment of EGCG could improve the healing of femoral bone defects and that this effect might be mediated at least in part by BMP-2 [20]. We hypothesized that local percutaneous injection of EGCG could promote fracture healing by enhancing BMP-2 expression

Experiment Animals
Tibial Fracture Model
Radiographic and μCT Analyses
Histological Study
Three Point Bending for Biomechanical Testing
Findings
Conclusions
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