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关节内注射 BM-MSCs 来源的外泌体在改善骨关节炎中的作用:// 轴的影响。

The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of // Axis.

机构信息

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, 4240310 Giza, Egypt.

Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, 4240310 Giza, Egypt.

出版信息

Discov Med. 2024 Jul;36(186):1420-1429. doi: 10.24976/Discov.Med.202436186.132.

Abstract

BACKGROUND

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 () and microRNA-21 () in the rat knee joints.

METHODOLOGY

Gene expression , , toll-like receptor-7 (), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness.

RESULTS

Our results showed that BM-MSCs-derived exosomes significantly elevated gene expression level ( < 0.05) along with subsequent downregulation of and ( < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( < 0.05).

CONCLUSION

Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.

摘要

背景

骨髓间充质干细胞(BM-MSCs)因其具有重要的抗炎和再生特性,最近受到了极大的关注。本研究旨在探讨关节内注射 BM-MSCs 衍生的外泌体对大鼠骨关节炎(OA)进展的治疗作用,并探讨大鼠膝关节中 Yes 相关蛋白 1()的环状 RNA 与 microRNA-21()之间的相互作用。

方法

通过定量逆转录聚合酶链反应(qRT-PCR)评估大鼠关节组织中的基因表达、、Toll 样受体 7()、聚集蛋白聚糖和 II 型胶原。此外,还采用酶联免疫吸附试验(ELISA)技术评估了炎症标志物白细胞介素 4(IL-4)、白细胞介素 10(IL-10)、白细胞介素 1β(IL-1β)和肿瘤坏死因子-α(TNF-α)以及氧化应激标志物谷胱甘肽(GSH)、丙二醛(MDA)和总活性氧(ROS)的水平。还对大鼠关节组织进行了苏木精和伊红(H&E)染色的组织病理学检查,并评估了关节软骨厚度。

结果

我们的结果表明,BM-MSCs 衍生的外泌体显著提高了基因表达水平(<0.05),同时下调了和(<0.05)。这些作用影响了大鼠关节表面的炎症环境,其中促炎和氧化应激标志物显著减少(<0.05),抗炎和抗氧化标志物显著增加(<0.05)。治疗组中聚集蛋白聚糖和 II 型胶原基因表达也显著升高(<0.05)。

结论

这些数据表明,BM-MSCs 衍生的外泌体在减轻 OA 症状和病理进展方面具有重要作用,可能被视为 OA 的一种有效且可接受的治疗选择。

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