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GelMA 水凝胶作为蛇床子素治疗类风湿关节炎的有前途的递药系统：靶向 miR-1224-3p/AGO1 轴。

GelMA Hydrogel as a Promising Delivery System for Osthole in the Treatment of Rheumatoid Arthritis: Targeting the miR-1224-3p/AGO1 Axis.

机构信息

Department of Spinal Degeneration and Deformity Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

出版信息

Int J Mol Sci. 2023 Aug 25;24(17):13210. doi: 10.3390/ijms241713210.

DOI:10.3390/ijms241713210
PMID:37686018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10488209/
Abstract

Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1β. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment.

摘要

类风湿性关节炎（RA）是一种多方面的、慢性的、进行性的自身免疫性疾病。本研究旨在探讨利用优化的明胶甲基丙烯酰（GelMA）载体增强药物传递系统在 RA 管理中的潜在益处。我们使用 qPCR、WB 和免疫荧光法评估了 RA 组织和细胞系中 miR-1124-3p 和 AGO1 的水平。通过 qPCR、H&E 染色和 micro-CT 评估蛇床子素对炎症反应和关节形态的影响。数据表明，miR-1224-3p 在 RA 组织和 HUM-iCell-s010RA 细胞中表达下调，而 HUM-iCell-s010RA 细胞中 miR-1224-3p 的过表达降低了 IL-6 和 IL-1β 的表达。荧光素酶测定表明 AGO1 是 miR-1224-3p 的直接靶基因。此外，蛇床子素处理增加了 miR-1224-3p 的水平并降低了 AGO1 的表达。释放数据表明，载有蛇床子素的 GelMA 的释放速度比游离蛇床子素慢。在 CIA 小鼠模型中的进一步研究证实，载有蛇床子素的 GelMA 更有效地减轻 RA 中的骨质疏松症和缓解自身免疫性关节炎。这些发现表明，蛇床子素可以调节 RASFs 细胞中的 miR-1224-3p/AGO1 轴，并有可能开发为临床抗 RA 药物。GelMA 可为长期 RA 治疗提供新途径。

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