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人骨髓间充质干细胞来源的外泌体抑制白细胞介素-1β诱导的骨关节炎软骨细胞炎症。

Human Bone Mesenchymal Stem Cell-Derived Exosomes Inhibit IL-1β-Induced Inflammation in Osteoarthritis Chondrocytes.

作者信息

Zhou Liping, Ye Haiwei, Liu Lizhen, Chen Yunhua

机构信息

Chemical Pharmaceutical Research Institute, Taizhou Vocational and Technical College, Taizhou, Zhejiang, China. Email:

Chemical Pharmaceutical Research Institute, Taizhou Vocational and Technical College, Taizhou, Zhejiang, China.

出版信息

Cell J. 2021 Sep;23(4):485-494. doi: 10.22074/cellj.2021.7127. Epub 2021 Aug 29.

Abstract

OBJECTIVE

Human bone marrow mesenchymal stem cell (hBMSC)-derived exosomes exhibit protective effects against inflammatory diseases. This study aimed to explore the effects of hBMSC-derived exosomes on osteoarthritis (OA) and its related mechanisms.

MATERIALS AND METHODS

In this experimental study, we characterised exosomes derived from hBMSCs by transmission electron microscopy, nanoparticle tracking and Western blot analysis. Cellular uptake of exosomes was observed by fluorescent microscopy. Cell viability of chondrocytes exposed to interleukin-1 beta (IL-1β) was determined by the Cell Counting Kit-8 (CCK-8). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine expression levels of genes related to apoptosis, inflammation, cartilage collagen metabolism and mitogen-activated protein kinases.

RESULTS

Fluorescence microscopy revealed that hBMSC-derived exosomes could be taken up by chondrocytes. hBMSC-derived exosomes could significantly enhance cell viability of chondrocytes in response to IL-1β treatment. RT-qPCR showed significant up-regulation of and expression levels by IL-1β treatment, while their mRNA expression levels decreased after coculture with exosomes. The anti-inflammatory gene was markedly suppressed by treatment; however, we observed its expression after co-culture with exosomes. Additionally, the pro-inflammatory genes displayed significantly elevated expression levels in the IL-1β group and reduced expression levels after co-culture with exosomes.

CONCLUSION

hBMSC-derived exosomes may play a protective role in chondrocytes through inhibiting cell apoptosis and the inflammatory response. These results will provide a novel therapeutic strategy for OA.

摘要

目的

人骨髓间充质干细胞(hBMSC)来源的外泌体对炎症性疾病具有保护作用。本研究旨在探讨hBMSC来源的外泌体对骨关节炎(OA)的影响及其相关机制。

材料与方法

在本实验研究中,我们通过透射电子显微镜、纳米颗粒追踪和蛋白质免疫印迹分析对hBMSC来源的外泌体进行了表征。通过荧光显微镜观察外泌体的细胞摄取情况。使用细胞计数试剂盒-8(CCK-8)测定暴露于白细胞介素-1β(IL-1β)的软骨细胞的细胞活力。采用实时定量聚合酶链反应(RT-qPCR)测定与细胞凋亡、炎症、软骨胶原代谢和丝裂原活化蛋白激酶相关的基因表达水平。

结果

荧光显微镜显示hBMSC来源的外泌体可被软骨细胞摄取。hBMSC来源的外泌体可显著提高经IL-1β处理的软骨细胞的细胞活力。RT-qPCR显示,IL-1β处理后 和 的表达水平显著上调,而与外泌体共培养后其mRNA表达水平降低。抗炎基因 经 处理后明显受到抑制;然而,与外泌体共培养后我们观察到了它的表达。此外,促炎基因 在IL-1β组中显示出显著升高的表达水平,与外泌体共培养后表达水平降低。

结论

hBMSC来源的外泌体可能通过抑制细胞凋亡和炎症反应对软骨细胞发挥保护作用。这些结果将为OA提供一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecc0/8405079/a2041491896f/Cell-J-23-485-g01.jpg

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