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miR-144-3p 通过靶向 IL-1β 改善骨关节炎的进展:潜在的治疗意义。

miR-144-3p ameliorates the progression of osteoarthritis by targeting IL-1β: Potential therapeutic implications.

机构信息

Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.

Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.

出版信息

J Cell Physiol. 2021 Oct;236(10):6988-7000. doi: 10.1002/jcp.30361. Epub 2021 Mar 27.

Abstract

The pro-inflammatory cytokine interleukin 1 beta (IL-1β) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL-mediated degradation of cartilage type II collagen. Previous studies have indicated that miR-144-3p is a useful target in the regulation of pro-inflammatory cytokines in different diseases. However, the role of miR-144-3p in OA is unclear. In this study, we observed a negative correlation between miR-144-3p and IL-1β expression in OA. miR-144-3p mimic transfection of OA synovial fibroblasts downregulated levels of IL-1β expression, while blocking the MAPK, PI3K/Akt, and NF-κB signaling pathways relating to IL-1β production, and effectively increased miR-144-3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR-144-3p mimic effectively ameliorated OA progression and reduced the numbers of IL-1β-positive cells in synovial tissue. This study suggests that miR-144-3p is a useful therapeutic target in OA disease.

摘要

促炎细胞因子白细胞介素 1β(IL-1β)在骨关节炎(OA)发病机制中起关键作用。微 RNA(miRNA)活性与 OA 中的炎症有关,某些 miRNA 特异性调节 IL 介导的软骨型 II 型胶原降解。先前的研究表明,miR-144-3p 是调节不同疾病中促炎细胞因子的有用靶标。然而,miR-144-3p 在 OA 中的作用尚不清楚。在这项研究中,我们观察到 OA 中 miR-144-3p 与 IL-1β表达之间存在负相关。OA 滑膜成纤维细胞中转染 miR-144-3p 模拟物可下调 IL-1β表达水平,同时阻断与 IL-1β产生有关的 MAPK、PI3K/Akt 和 NF-κB 信号通路,并且可以有效地增加 OASFs 中的 miR-144-3p 表达。前交叉韧带切断大鼠模型的研究结果表明,给予 miR-144-3p 模拟物可有效改善 OA 进展并减少滑膜组织中 IL-1β阳性细胞的数量。这项研究表明,miR-144-3p 是 OA 疾病的一个有用的治疗靶点。

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