Cyasterone accelerates fracture healing by promoting MSCs migration and osteogenesis

Junlang Zhu; Yamei Liu; Chen Chen; Hongtai Chen; Jiewen Huang; Yiwen Luo; Kewei Zhao; Dongfeng Chen; Zhiming Xu; Wangyang Li; Xunchao Zhang; Yunpu Xiong; Liangliang Xu; Bin Wang

doi:10.1016/j.jot.2020.11.004

Cyasterone accelerates fracture healing by promoting MSCs migration and osteogenesis

J Orthop Translat. 2021 Feb 19:28:28-38. doi: 10.1016/j.jot.2020.11.004. eCollection 2021 May.

Authors

Junlang Zhu¹, Yamei Liu^{2

3}, Chen Chen^{2

3}, Hongtai Chen⁴, Jiewen Huang¹, Yiwen Luo¹, Kewei Zhao⁵, Dongfeng Chen², Zhiming Xu⁶, Wangyang Li⁷, Xunchao Zhang¹, Yunpu Xiong⁸, Liangliang Xu⁹, Bin Wang¹

Affiliations

¹ Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510240, PR China.
² College of Basic Medical, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
³ Innovative Research & Development Lab. of TCM, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
⁴ Department of Orthopaedics and Traumatology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, Hong Kong SAR, 999077, PR China.
⁵ Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510240, PR China.
⁶ Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, 529000, PR China.
⁷ The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410208, PR China.
⁸ Department of Orthopaedics, Guangzhou Orthopedic Hospital, Guangzhou, 510030, PR China.
⁹ Lingnan Medical Research Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China.

Abstract

Background: Mesenchymal Stem Cells (MSCs) therapy has become a new coming focus of clinical research in regenerative medicine. However, only a small number of implanted MSCs could successfully reach the injured areas. The previous studies have shown that fracture healing time is inversely proportional to concentration of MSCs in injured tissue.

Methods: The migration and osteogenesis of MSCs were assessed by transwell assay and Alizarin Red S staining. Levels of gene and protein expression were checked by qPCR and Western Blot. On the other hand, the enhanced migration ability of MSCs induced by Cyasterone was retarded by CXCR4 siRNA. In addition, the rat model of femoral fracture was established to evaluate the effect of Cyasterone on fracture healing. What's more, we also checked the effect of Cyasterone on mobilisation of MSCs in vivo.

Results: The results showed that Cyasteron increased the number of MSCs in peripheral blood. The concentrations of SDF-1α in serum at different time points were determined by ELISA assay. Micro-CT and histological analysis were used to evaluate the fractured femurs.Our results showed that Cyasterone could promote the migration and osteogenesis capacities of MSCs. The fractured femurs healed faster with treatment of Cyasterone. Meanwhile, Cyasterone could significantly increase the level of SDF-1α in rats with femur fracture.

Conclusion: Cyasterone could promote migration and osteogenesis of MSCs, and most importantly, it could accelerate bone fracture healing.Translational Potential statement: These findings provide evidence that Cyasterone could be used as a therapeutic reagent for MSCs mobilisation and osteogenesis. What's more, it could acclerate fracture healing.

Keywords: Cyasterone; Fracture; MSCs; Osteogenesis; SDF-1α.