Bushenhuoxue formula accelerates fracture healing via upregulation of TGF-β/Smad2 signaling in mesenchymal progenitor cells.

Jun 15, 2020

Contributor: Songfeng Hu,Qinwen Ge,Chenjie Xia,Jun Ying,Hongfeng Ruan,Zhenyu Shi,Rui Xu,Taotao Xu,Shuaijie Lv,Liang Fang,Zhen Zou,Huihui Xu,Luwei Xiao,Peijian Tong,Ping-Er Wang,Hongting Jin

Although Bushenhuoxue formula (BSHXF) is successfully used as a non-traumatic therapy in treating bone fracture in China, the molecular mechanism underlying its effects remains poorly understood.
The present study aims to explore the therapeutic effects of BSHXF on fracture healing in mice and the underlying mechanism.
We performed unilateral open transverse tibial fracture procedure in C57BL/6 mice which were treated with or without BSHXF. Fracture callus tissues were collected and analyzed by X-ray, micro-CT, biomechanical testing, histopathology and quantitative gene expression analysis. Tibial fracture procedure was also performed in Cre-negative and Gli1-CreER; Tgfbr2flox/flox conditional knockout (KO) mice (Tgfbr2) to determine if BSHXF enhances fracture healing in a TGF-β-dependent manner. In addition, scratch-wound assay and cell counting kit-8 (CCK-8) assay were used to evaluate the effect of BSHXF on cell migration and cell proliferation in C3H10T1/2 mesenchymal stem cells, respectively.
BSHXF promoted endochondral ossification and enhanced bone strength in wild-type (WT) or Cre- control mice. In contrast, BSHXF failed to promote bone fracture healing in Tgfbr2 conditional KO mice. In the mice receiving BSHXF treatment, TGF-β/Smad2 signaling was significantly activated. Moreover, BSHXF enhanced cell migration and cell proliferation in C3H10T1/2 cells, which was strongly attenuated by the small molecule inhibitor SB525334 against TGF-β type I receptor.
These data demonstrated that BSHXF promotes fracture healing by activating TGF-β/Smad2 signaling. BSHXF may be used as a type of alternative medicine for the treatment of bone fracture healing.

Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.

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About The Expert

Songfeng Hu

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; Department of Orthopaedics and Traumatology, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing 312000, Zhejiang, China.

Qinwen Ge

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Chenjie Xia

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Jun Ying

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Hongfeng Ruan

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Zhenyu Shi

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Rui Xu

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Taotao Xu

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.

Shuaijie Lv

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.

Liang Fang

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Zhen Zou

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Huihui Xu

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Luwei Xiao

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Peijian Tong

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.

Ping-Er Wang

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. Electronic address: apple63209321@126.com.

Hongting Jin

Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. Electronic address: hongtingjin@163.com.

References

PubMed