Radix Rehmanniae Praeparata promotes bone fracture healing through activation of TGF-β signaling in mesenchymal progenitors
Rui Xu, Cheng Luo, Qinwen Ge, Jun Ying, Peng Zhang, Chenjie Xia, Liang Fang, Huihui Xu, Wenhua Yuan, Taotao Xu, Shuaijie Lv, Hongting Jin, Peijian Tong, Kun Tian, Pinger Wang
Abstract
Radix Rehmanniae Praeparata (RR), the steamed roots of Rehmannia glutinosa, is a traditional Chinese medicine with the function of kidney-nourishing, and it has been safety used for centuries to treat bone-related disorders. The aim of this study is to investigate the positive effect and underlying mechanism of RR enhancing bone fracture healing in mouse model. Ten-week-old C57BL/6J mice were subjected to a unilateral open transverse tibial fracture and provided a daily treatment of RR. Bone samples were harvested for tissue analyses including x-ray, μCT, histology, histomorphometry, biomechanical testing, immunohistochemical (IHC) and quantitative gene expression analysis. To determine the role of TGF-β in accelerating fracture healing effect of RR, aforementioned experiments were performed on Gli1-CreER; Tgfbr2 flox/flox (Tgfbr2Gli1ER) conditional knockout mice. RR promoted bone fracture healing and strengthened bone intensity in wild-type and Cre− mice with the activation of TGF-β/Smad2 signaling, on the contrary, RR failed to accelerating fracture healing in Tgfbr2Gli1ER mice. RR promotes bone fracture healing by intensify the contribution of Gli1+ cells on bone and cartilage formation mainly in TGF-β-dependent manner. RR is an alternative option for clinical treatment of fracture.