Zhu Junlang, Liu Yamei, Chen Chen, Chen Hongtai, Huang Jiewen, Luo Yiwen, Zhao Kewei, Chen Dongfeng, Xu Zhiming, Li Wangyang, Zhang Xunchao, Xiong Yunpu, Xu Liangliang, Wang Bin
Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510240, PR China.
College of Basic Medical, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
J Orthop Translat. 2021 Feb 19;28:28-38. doi: 10.1016/j.jot.2020.11.004. eCollection 2021 May.
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.
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.
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.
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.
间充质干细胞（MSCs）疗法已成为再生医学临床研究的新热点。然而，仅有少量植入的间充质干细胞能够成功抵达损伤部位。先前的研究表明，骨折愈合时间与损伤组织中间充质干细胞的浓度成反比。
通过Transwell实验和茜素红S染色评估间充质干细胞的迁移和成骨能力。采用qPCR和蛋白质免疫印迹法检测基因和蛋白质表达水平。另一方面，CXCR4小干扰RNA可抑制赛司他汀诱导的间充质干细胞迁移能力增强。此外，建立大鼠股骨骨折模型以评估赛司他汀对骨折愈合的影响。而且，我们还检测了赛司他汀对体内间充质干细胞动员的影响。
结果显示，赛司他汀可增加外周血中间充质干细胞的数量。采用ELISA法测定不同时间点血清中SDF-1α的浓度。运用Micro-CT和组织学分析评估股骨骨折情况。我们的结果表明，赛司他汀可促进间充质干细胞的迁移和成骨能力。经赛司他汀治疗后，股骨骨折愈合加快。同时，赛司他汀可显著提高股骨骨折大鼠体内SDF-1α的水平。
赛司他汀可促进间充质干细胞的迁移和成骨，最重要的是，它可加速骨折愈合。转化潜力声明：这些发现提供了证据，表明赛司他汀可作为一种用于间充质干细胞动员和成骨的治疗试剂。此外，它可加速骨折愈合。
