Dexamethasone-Activated MSCs Release MVs for Stimulating Osteogenic Response.

Dexamethasone-Activated MSCs Release MVs for Stimulating Osteogenic Response.
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地塞米松激活的 MSC 释放 MV 来刺激成骨反应

DOI:
10.1155/2018/7231739
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发表时间:
2018
影响因子:
4.3
通讯作者:
Lin H
Lin H
中科院分区:
医学3区
文献类型:
--
作者:
Zhao M;Li P;Xu H;Pan Q;Zeng R;Ma X;Li Z;Lin H

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细胞外微泡(MV)引起了人们的广泛关注,因为它们被发现是参与组织再生的关键旁分泌介质。地塞米松 (DXM) 被广泛认为是调节间充质干细胞 (MSC) 分化潜力的重要调节剂。然而,DXM 对 MSC 旁分泌信号传导的影响仍不清楚。为此,我们的目的是根据 MSC-MV 的理化特性和对成骨反应的支持,通过评估 MSC-MV 的释放和功能,探讨 DXM 在调节 MSC 旁分泌活性中的作用。结果表明,DXM对MSC-MVs的释放没有明显影响,但在调节MSC-MVs的功能方面发挥着关键作用。从 DXM 刺激的 MSC (DXM-MV) 获得的 MV 增加了 MC3T3 细胞增殖和迁移,并上调 Runt 相关转录因子 2 (Runx2)、碱性磷酸酶 (ALP) 和骨桥蛋白 (OPN) 的表达。在已建立的大鼠模型中进一步研究了 DXM-MV 对股骨缺损的修复效率。研究发现,DXM-MVs 加速了缺损区域骨形成的愈合过程。因此,我们得出结论,使用 DXM 作为刺激来获得功能性 MSCs-MV 可能成为促进骨再生的有价值的工具。
The extracellular microvesicles (MVs) are attracting much attention because they are found to be the key paracrine mediator participating in tissue regeneration. Dexamethasone (DXM) is widely accepted as an important regulator in tailoring the differentiation potential of mesenchymal stem cells (MSCs). However, the effect of DXM on the paracrine signaling of MSCs remains unknown. To this point, we aimed to explore the role of DXM in regulating the paracrine activity of MSCs through evaluating the release and function of MSC-MVs, based on their physicochemical characteristics and support on osteogenic response. Results showed that DXM had no evident impact on the release of MSC-MVs but played a pivotal role in regulating the function of MSC-MVs. MVs obtained from the DXM-stimulated MSCs (DXM-MVs) increased MC3T3 cell proliferation and migration and upregulated Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteopontin (OPN) expression. The repair efficiency of DXM-MVs for femur defects was further investigated in an established rat model. It was found that DXM-MVs accelerated the healing process of bone formation in the defect area. Thus, we conclude that using DXM as stimuli to obtain functional MSCs-MVs could become a valuable tool for promoting bone regeneration.
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