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微电流刺激可抑制白细胞介素-1β诱导的软骨细胞炎症反应,并保护膝关节骨软骨免受骨关节炎的侵害。

Micro-current stimulation could inhibit IL-1β-induced inflammatory responses in chondrocytes and protect knee bone cartilage from osteoarthritis.

作者信息

Lee Minjoo, Lee Hana, Chung Halim, Lee Jin-Ho, Kim Doyong, Cho Seungkwan, Kim Tack-Joong, Kim Han Sung

机构信息

Department of Biomedical Engineering, Yonsei University, Gangwon, 26493 South Korea.

Division of Biological Science and Technology, Yonsei University, Gangwon, 26493 South Korea.

出版信息

Biomed Eng Lett. 2024 Apr 17;14(4):801-812. doi: 10.1007/s13534-024-00376-1. eCollection 2024 Jul.

Abstract

This study aimed to evaluate the inhibitory effects of micro-current stimulation (MCS) on inflammatory responses in chondrocytes and degradation of extracellular matrix (ECM) in osteoarthritis (OA). To determine the efficacy of MCS, IL-1β-treated chondrocytes and monosodium iodoacetate (MIA)-induced OA rat model were used. To evaluate the cytotoxicity and nitric oxide (NO) production in SW1353 cells, the presence or absence of IL-1β treatment or various levels of MCS were applied. Immunoblot analysis was conducted to evaluate whether MCS can modulate IL-1R1/MyD88/NF-κB signaling pathway and various indicators involved in ECM degradation. Additionally, to determine whether MCS alleviates subchondral bone structure destruction caused by OA, micro-CT analysis, immunoblot analysis, and ELISA were conducted using OA rat model. 25 and 50 µA levels of MCS showed effects in cell proliferation and NO production. The MCS group with IL-1β treatment lead to significant inhibition of protein expression levels regarding IL-1R1/MyD88/NF-κB signaling and reduction of the nucleus translocation of NF-κB. In addition, the protein expression levels of MMP-1, MMP-3, MMP-13, and IL-1β decreased, whereas collagen II and aggrecan increased. In animal results, morphological analysis of subchondral bone using micro-CT showed that MCS induced subchondral bone regeneration and improvement, as evidenced by increased thickness and bone mineral density of the subchondral bone. Furthermore, MCS-applied groups showed decreases in the protein expression of MMP-1 and MMP-3, while increases in collagen-II and aggrecan expressions. These findings suggest that MCS has the potential to be used as a non-pharmaceutical method to alleviate OA.

摘要

本研究旨在评估微电流刺激(MCS)对骨关节炎(OA)中软骨细胞炎症反应及细胞外基质(ECM)降解的抑制作用。为确定MCS的疗效,使用了白细胞介素-1β(IL-1β)处理的软骨细胞和碘乙酸钠(MIA)诱导的OA大鼠模型。为评估SW1353细胞中的细胞毒性和一氧化氮(NO)生成,应用了有无IL-1β处理或不同水平的MCS。进行免疫印迹分析以评估MCS是否能调节IL-1R1/MyD88/NF-κB信号通路及参与ECM降解的各种指标。此外,为确定MCS是否能减轻OA引起的软骨下骨结构破坏,使用OA大鼠模型进行了显微CT分析、免疫印迹分析和酶联免疫吸附测定(ELISA)。25和50微安水平的MCS对细胞增殖和NO生成有影响。IL-1β处理的MCS组导致IL-1R1/MyD88/NF-κB信号相关蛋白表达水平显著抑制,且NF-κB核转位减少。此外,基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-13(MMP-13)和IL-1β的蛋白表达水平降低,而Ⅱ型胶原和聚集蛋白聚糖增加。在动物实验结果中,使用显微CT对软骨下骨进行形态学分析表明,MCS诱导了软骨下骨再生和改善,软骨下骨厚度和骨密度增加证明了这一点。此外,应用MCS的组MMP-1和MMP-3的蛋白表达降低,而Ⅱ型胶原和聚集蛋白聚糖表达增加。这些发现表明,MCS有潜力作为一种非药物方法来缓解OA。

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