Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.

IF 3.3 4区医学 Q3 IMMUNOLOGY Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-07-15 DOI:10.1080/08916934.2024.2361749

Chunlei He, Zhaogan Zeng, Yadong Yang, Shanshan Ye, Qiang Wu, Xunzhi Liu, Chenghong Liu, Wanhui Zeng, Sheng Liu

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Abstract

Background: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression.

Objective: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes.

Methods: Chondrocytes were treated with interleukin (IL)-1β to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay.

Results: CircTRIM25 was upregulated in OA tissues and IL-1β-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1β-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo.

Conclusion: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

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沉默CircTRIM25/miR-138-5p/CREB1轴可促进骨关节炎中的软骨生成。

背景：失调的环状 RNA（circRNA）参与了骨关节炎（OA）的进展：我们旨在探讨 hsa_circ_0044719 (circTRIM25) 对软骨细胞铁变态反应的影响：方法：用白细胞介素（IL）-1β处理软骨细胞，生成细胞模型。使用细胞计数试剂盒-8、酶联免疫吸附试验、相关试剂盒、碘化丙啶染色和免疫荧光试验测量细胞行为。采用定量实时聚合酶链反应检测了 circTRIM25、miR-138-5p 和 cAMP 反应元件结合蛋白 1（CREB1）的表达，并使用荧光素酶报告分析和 RNA 牵引试验评估了它们之间的相互作用：结果：CircTRIM25在OA组织和IL-1β刺激的软骨细胞中上调。敲除circTRIM25可提高IL-1β诱导细胞的存活率，抑制其铁蛋白沉积和炎症反应。CircTRIM25是miR-138-5p的海绵，而miR-138-5p直接靶向CREB1。miR-138-5p的下调会减弱circTRIM25敲除所诱导的效应。此外，加强 CREB1 可逆转 miR-138-5p 的诱导效应。此外，circTRIM25的敲除可减轻体内软骨损伤：结论：沉默circTRIM25可通过miR-138-5p/CREB轴抑制软骨细胞的铁凋亡，从而减轻OA的进展。

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

Autoimmunity 医学-免疫学

CiteScore

5.70

自引率

8.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.