Stearic acid methyl ester promotes migration of mesenchymal stem cells and accelerates cartilage defect repair
Stearic acid methyl ester promotes migration of mesenchymal stem cells and accelerates cartilage defect repair
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DOI：
10.1016/j.jot.2019.09.008
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发表时间：
2020-05-01
影响因子：
6.6
通讯作者：
Li, Gang
中科院分区：
文献类型：
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作者：
Liu, Yamei;Xu, Liangliang;Li, Gang
背景资料：骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有多向分化潜能，可向成骨、成软骨和成脂细胞分化。这些特性使骨髓间充质干细胞成为软骨缺损修复的理想细胞来源。炎症刺激可以募集MSCs，然后归巢到损伤组织。然而，其归航能力极为有限。因此，开发可用于增强MSC归巢效率的试剂或方法变得非常必要。本研究探讨硬脂酸甲酯（硬脂酸甲酯）对骨髓间充质干细胞动员和软骨再生的影响。方法：分离培养SD大鼠股骨间充质干细胞。MTT法检测顺铂对骨髓间充质干细胞活力的影响。采用Transwell法和创伤愈合法检测顺铂对MSCs迁移的影响。通过RNA-seq、实时定量PCR和western blot分析RNA和蛋白质的表达。采用集落形成实验和流式细胞仪检测细胞因子对骨髓间充质干细胞动员的影响。建立大鼠软骨缺损模型，以评价骨水泥对软骨再生的影响。结果：发现甘草酸可促进骨髓间充质干细胞迁移。有趣的是，我们发现在MSC中，Vav 1的表达水平显著增加。另一方面，Vav 1小干扰RNA（siRNA）和Rho相关蛋白激酶2（ROCK 2）抑制剂可抑制LPS诱导的MSCs迁移能力的增强。此外，我们还检查了在体内的MSC的动员的影响。结果表明，黄芪能增加骨髓间充质干细胞在外周血中的数量，增强骨髓间充质干细胞集落形成能力。最后，使用大鼠软骨缺损模型，我们发现骨水泥可以改善软骨修复。结论：我们的研究表明，BMSCs主要通过Vav 1/ROCK 2信号通路增强MSCs的迁移能力，这可能有助于加速软骨再生。这篇文章的翻译潜力：这些发现提供了证据，证明BMSCs可用作MSC动员和软骨再生的治疗试剂。
Background: Mesenchymal stem cells (MSCs) can be easily expanded without losing the ability of multilineage differentiation, including oesteogenic, chondrogenic and adipogenic differentiation. These characters make MSCs a promising cell resource for cartilage defect repair. MSCs could be recruited by inflammatory stimulation, then home to the injury tissues. However, its capacity of homing is extremely limited. Thus, it has become extremely necessary to develop an agent or a method, which can be used to enhance the efficiency of MSCs homing. This study investigates the effect of stearic acid methyl ester (SAME) on MSCs mobilisation and cartilage regeneration. Methods: MSCs were isolated from femurs of Sprague-Dawley (SD) rats. MTT assay was used to detect effect of SAME on viability of MSCs. Transwell assay and wound healing assay were used to detect effect of SAME on migration of MSCs. RNA-seq, quantitative real-time PCR and western blot were performed to analyze the expression of RNAs and proteins. Colony forming assay and flow cytometry were used to evaluate the effect of SAME on MSCs mobilisation in vivo. A rat cartilage defect model was created to evaluate the effect of SAME on cartilage regeneration. Results: We found that SAME could promote the migration of MSCs. Interestingly, we found SAME significantly increased the expression levels of Vav1 in MSCs. On the other hand, the enhanced migration ability of MSCs induced by SAME was retarded by Vav1 small interfering RNA (siRNA) and Rho-associated protein kinase 2 (ROCK2) inhibitor. In addition, we also checked the effect of SAME on mobilisation of MSCs in vivo. The results showed that SAME increased the number of MSCs in peripheral blood and enhanced the capacity of colony formation. Finally, using a cartilage defect model in rats, we found SAME could improve cartilage repair. Conclusion: Our study demonstrates that SAME can enhance MSCs migration ability mainly through the Vav1/ ROCK2 signaling pathway, which could contribute to the accelerated cartilage regeneration. The translational potential of this article: These findings provide evidence that SAME could be used as a therapeutic reagent for MSCs mobilisation and cartilage regeneration.