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

Biomedicine & Pharmacotherapy (Oct 2020)

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

Affiliations

Rui Xu: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Cheng Luo: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, China
Qinwen Ge: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Jun Ying: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Peng Zhang: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Chenjie Xia: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Liang Fang: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Huihui Xu: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Wenhua Yuan: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Taotao Xu: Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Shuaijie Lv: The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Hongting Jin: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Peijian Tong: Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Kun Tian: Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding authors.
Pinger Wang: Institute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Corresponding authors.

Journal volume & issue: Vol. 130
p. 110581

Abstract

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Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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