研究动态
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在骨关节炎中,Notopterol 通过 JAK2/NF-kB/hsa-miR-4282 途径阻断 NLRP3 炎性体,从而减轻 IL-1β 引发的细胞焦亡。

Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis.

发表日期:2024 Mar 30
作者: Ko-Ta Chen, Chi-Tai Yeh, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Iat-Hang Fong, Wei-Hwa Lee, Yen-Shuo Chiu
来源: ARTHRITIS RESEARCH & THERAPY

摘要:

骨关节炎 (OA) 是最常见的关节炎形式,影响 60 岁以上大约 10% 的男性和 18% 的女性。目前,彻底治愈 OA 仍难以实现,这给临床管理带来了挑战。传统中药羌活是治疗风湿病的蠲痹丸的组成部分,通过其强大的抗炎作用显示出保护软骨细胞的前景。为了探索羌活醇和 miRNA (has-miR-4248) 对炎症的保护作用,我们模拟了软骨细胞细胞系 C20A4 和 C28/12 中的炎症环境,重点是炎症小体形成和细胞焦亡。我们的研究结果表明,诺蝶醇显着降低炎症细胞中白细胞介素 (IL)-18 和肿瘤坏死因子 (TNF)-α 的水平,减少活性氧 ( ROS)在炎症后产生,并抑制 JAK2/STAT3 信号通路,从而保护软骨细胞免受炎症影响。重要的是,Notopterol 还通过 hsa-miR-4282 调节阻断 NF-κB/NLRP3 通路,从而阻碍炎症小体组装和细胞焦亡。体内实验表明,与对照组相比,羌活醇治疗显着降低了 OA 小鼠的国际骨关节炎研究协会 (OARSI) 评分,并提高了 hsa-miR-4282 表达。这项研究强调了羌活醇作为 OA 治疗药物的潜力,强调了其在 OA 治疗中的潜力。保护软骨免受炎症引起的损伤,特别是通过防止细胞焦亡。© 2024 作者。
Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects.To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis.Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups.This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.© 2024 The Authors.