TY - JOUR TI - Bushenhuoxue formula accelerates fracture healing via upregulation of TGF-β/Smad2 signaling in mesenchymal progenitor cells AU - Hu, Songfeng AU - Ge, Qinwen AU - Xia, Chenjie AU - Ying, Jun AU - Ruan, Hongfeng AU - Shi, Zhenyu AU - Xu, Rui AU - Xu, Taotao AU - Lv, Shuaijie AU - Fang, Liang AU - Zou, Zhen AU - Xu, Huihui AU - Xiao, Luwei AU - Tong, Peijian AU - Wang, Ping-er AU - Jin, Hongting T2 - Phytomedicine AB - Background 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. Purpose The present study aims to explore the therapeutic effects of BSHXF on fracture healing in mice and the underlying mechanism. Methods 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 (Tgfbr2Gli1ER) 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. Results 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 Tgfbr2Gli1ER 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. Conclusion 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. DA - 2020/09/01/ PY - 2020 DO - 10.1016/j.phymed.2020.153256 DP - ScienceDirect VL - 76 SP - 153256 J2 - Phytomedicine LA - en SN - 0944-7113 UR - http://www.sciencedirect.com/science/article/pii/S0944711320300878 Y2 - 2020/06/16/17:33:27 KW - Bushenhuoxue formula KW - Fracture healing KW - Mesenchymal progenitor cells KW - TGF-β signaling ER -