Exosomes of Human Fetal Cartilage Progenitor Cells (hFCPCs) Inhibited Interleukin-1β (IL-1β)-Induced Osteoarthritis Phenotype via miR-125b-5p In Vitro.

IF 4.4 4区 医学 Q2 CELL & TISSUE ENGINEERING
JuHyeok Lee, Jiyoung Lee, Byung Hyune Choi
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引用次数: 0

Abstract

Background: This study investigated anti-inflammatory effects of exosomes derived from human fetal cartilage progenitor cells (hFCPC-Exo) and their microRNAs (miRNAs) on the osteoarthritis (OA) phenotype in vitro in comparison with exosomes from bone marrow mesenchymal stem cells (MSC-Exo).

Methods: SW982 cells (synoviocytes) or hFCPCs (chondrocytes) were stimulated with 10 ng/mL IL-1β to mimic OA phenotypes. The effects of hFCPC-Exo and MSC-Exo were compared by measuring the expression of inflammatory cytokines and an anti-inflammatory protein. miRNA profiles of hFCPC-Exo and MSC-Exo were analyzed using a 2588 human miRNA dataset, and miRNAs potentially involved in the anti-inflammatory effect of hFCPC-Exo were selected. miRNA mimics and antisense inhibitors were used to investigate the role of selected miRNAs in the IL-1β signaling pathways.

Results: Both hFCPC-Exo and MSC-Exo significantly decreased the expression of inflammatory cytokines (IL-1β, IL-6, and MCP-1), while slightly increased an anti-inflammatory protein (SOCS1) in IL-1β-treated SW982 cells. miRNA sequencing revealed anti-inflammatory miRNAs present in large amounts in both hFCPC-Exo and MSC-Exo. Among them, miR-125b-5p mimic significantly suppressed the expression of inflammatory cytokines induced by IL-1β, while anti-sense inhibitor of miR-125b-5p efficiently blocked anti-inflammatory effects of hFCPC-Exo. Both hFCPC-Exo and miR-125b-5p inhibited IκBα down-regulation and -NF-κB stabilization in IL-1β-treated SW982 cells. Additionally, hFCPC-Exo and miR-125b-5p showed similar effects on IL-1β-treated hFCPCs as an OA model in chondrocytes by down-regulating the expression of IL-1β, MMP13, and ADAMTS-5 and up-regulating the expression of aggrecan (ACAN) and type II collagen (COL2A1).

Conclusion: This study demonstrated that hFCPC-Exo exhibits anti-inflammatory effects on IL-1β-treated synoviocytes and chondrocytes in vitro possibly by down-regulating the IL-1β-TRAF6-NF-κB pathway via anti-inflammatory miRNAs such as miR-125b-5p.

人胎儿软骨祖细胞(hfcpc)外泌体通过miR-125b-5p体外抑制IL-1β诱导的骨关节炎表型
背景:本研究通过与骨髓间充质干细胞外泌体(MSC-Exo)比较,研究了人胎儿软骨祖细胞外泌体(hFCPC-Exo)及其microRNAs (miRNAs)对骨关节炎(OA)表型的体外抗炎作用。方法:用10 ng/mL IL-1β刺激SW982细胞(滑膜细胞)或hfcpc细胞(软骨细胞),模拟OA表型。通过检测炎症因子和抗炎蛋白的表达,比较hFCPC-Exo和MSC-Exo的作用。使用2588个人类miRNA数据集分析hFCPC-Exo和MSC-Exo的miRNA谱,并选择可能参与hFCPC-Exo抗炎作用的miRNA。使用miRNA模拟物和反义抑制剂来研究选定的miRNA在IL-1β信号通路中的作用。结果:hFCPC-Exo和MSC-Exo均能显著降低IL-1β、IL-6和MCP-1的表达,而轻度升高IL-1β处理的SW982细胞的抗炎蛋白SOCS1的表达。miRNA测序显示,hFCPC-Exo和MSC-Exo中均存在大量抗炎miRNA。其中,miR-125b-5p mimic显著抑制IL-1β诱导的炎症细胞因子的表达,而miR-125b-5p反义抑制剂有效阻断hFCPC-Exo的抗炎作用。在il -1β处理的SW982细胞中,hfcp - exo和miR-125b-5p均抑制i -κB α下调和-NF-κB稳定。此外,hFCPCs - exo和miR-125b-5p通过下调IL-1β、MMP13和adamt -5的表达,上调聚集蛋白(ACAN)和II型胶原(COL2A1)的表达,对IL-1β处理的hFCPCs作为软骨细胞OA模型显示出类似的作用。结论:本研究表明,hFCPC-Exo可能通过miR-125b-5p等抗炎mirna下调IL-1β-TRAF6-NF-κB通路,在体外对il -1β处理的滑膜细胞和软骨细胞具有抗炎作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue engineering and regenerative medicine
Tissue engineering and regenerative medicine CELL & TISSUE ENGINEERING-ENGINEERING, BIOMEDICAL
CiteScore
6.80
自引率
5.60%
发文量
83
审稿时长
6-12 weeks
期刊介绍: Tissue Engineering and Regenerative Medicine (Tissue Eng Regen Med, TERM), the official journal of the Korean Tissue Engineering and Regenerative Medicine Society, is a publication dedicated to providing research- based solutions to issues related to human diseases. This journal publishes articles that report substantial information and original findings on tissue engineering, medical biomaterials, cells therapy, stem cell biology and regenerative medicine.
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