Volume 33, Issue 4 p. 5399-5410
Research
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Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

Tan Zhang

Tan Zhang

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

These authors contributed equally to this work.Search for more papers by this author
Weiqi Han

Weiqi Han

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

These authors contributed equally to this work.Search for more papers by this author
Kangxian Zhao

Kangxian Zhao

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

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Wanlei Yang

Wanlei Yang

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

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Xuanyuan Lu

Xuanyuan Lu

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

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Yewei Jia

Yewei Jia

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

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An Qin

An Qin

Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Yu Qian

Corresponding Author

Yu Qian

Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, China

Correspondence: Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, #568 Zhongxing North Rd., Shaoxing, Zhejiang 312000, China. E-mail: [email protected]

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First published: 31 January 2019
Citations: 36
This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information.

ABSTRACT

Bone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis, mRNA expression of osteoclast-specific genes, and osteoclastic bone resorption in primary bone marrow-derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen-induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen-treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). www.fasebj.org