Cyasterone accelerates fracture healing by promoting MSCs migration and osteogenesis.

Cyasterone accelerates fracture healing by promoting MSCs migration and osteogenesis.
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Cyasterone 通过促进 MSC 迁移和成骨来加速骨折愈合

DOI:
10.1016/j.jot.2020.11.004
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发表时间:
2021-05
影响因子:
6.6
通讯作者:
Wang B
Wang B
中科院分区:
医学2区
文献类型:
--
作者:
Zhu J;Liu Y;Chen C;Chen H;Huang J;Luo Y;Zhao K;Chen D;Xu Z;Li W;Zhang X;Xiong Y;Xu L;Wang B

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骨髓间充质干细胞(Mesenchymal stem cells,MSCs)治疗已成为再生医学临床研究的新热点。然而,只有少数植入的MSC可以成功到达损伤区域。以往的研究表明,骨折愈合时间与损伤组织中MSC的浓度成反比。通过transwell法和茜素红S染色观察MSCs的迁移和成骨能力。通过qPCR和蛋白质印迹检查基因和蛋白质表达水平。CXCR 4 siRNA抑制了Cyasterone诱导的MSCs迁移能力的增强。另外,建立大鼠股骨骨折模型,观察杯甾酮对骨折愈合的影响。此外,我们还检查了杯甾酮对体内MSC动员的影响。结果表明,Cyasteron可增加外周血中MSC的数量。采用ELISA法测定不同时间点血清中SDF-1α的浓度。显微CT和组织学观察显示,杯甾酮能促进骨髓间充质干细胞的迁移和成骨能力。骨折的股骨愈合更快的治疗Cyasterone。同时,Cyasterone可显著提高骨折大鼠血清SDF-1α水平。杯甾酮能促进MSCs的迁移和成骨,最重要的是能促进骨折愈合。翻译潜力声明:这些发现提供了证据表明,杯甾酮可用作MSC动员和成骨的治疗剂。更重要的是,它可以加速骨折愈合。
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.
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