Cyclic strain-induced chondrocyte damage is actively involved in the pathogenesis of osteoarthritis and arthritis. MicroRNAs (miRNAs) carried by exosomes have been implicated in various diseases. However, the role of miR-100-5p in cyclic strain-induced chondrocyte damage remains to be elucidated. miR-100-5p and NADPH oxidase 4 (NOX4) were silenced or overexpressed in human primary articular chondrocytes. PKH-67 Dye was used to trace exosome endocytosis. Reactive oxygen species (ROS) production was monitored using DCFH-DA. Cell apoptosis was measured using a flow cytometer. Quantitative RT-PCR and Western blots were used to evaluate gene expression. Cyclic strain promoted ROS production and apoptosis in primary articular chondrocytes in a time-dependent manner. HucMSCs-derived exosomal miR-100-5p inhibited cyclic strain-induced ROS production and apoptosis in primary articular chondrocytes. miR-100-5p directly targeted NOX4. Overexpressing NOX4 attenuated hucMSCs-derived exosomes-mediated protective effects in primary articular chondrocytes. Cyclic strain promotes ROS production and apoptosis in primary articular chondrocytes, which was abolished by hucMSCs-derived exosomal miR-100-5p through its target NOX4. The findings highlight the importance of miR-100-5p/NOX4 axis in primary articular chondrocytes injury and provide new insights into therapeutic strategies for articular chondrocytes injury and osteoarthritis.

中文翻译：

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来自人脐带间充质干细胞的外泌体通过 miR-100-5p/NOX4 轴抑制人关节软骨细胞中 ROS 的产生和细胞凋亡

循环应变诱导的软骨细胞损伤积极参与骨关节炎和关节炎的发病机制。外泌体携带的微小RNA（miRNA）与各种疾病有关。然而，miR-100-5p 在循环应变诱导的软骨细胞损伤中的作用仍有待阐明。miR-100-5p 和 NADPH 氧化酶 4 (NOX4) 在人原代关节软骨细胞中被沉默或过表达。PKH-67 Dye 用于追踪外泌体内吞作用。使用 DCFH-DA 监测活性氧 (ROS) 的产生。使用流式细胞仪测量细胞凋亡。定量 RT-PCR 和蛋白质印迹用于评估基因表达。环状菌株以时间依赖性方式促进原代关节软骨细胞中 ROS 的产生和凋亡。HucMSCs 衍生的外泌体 miR-100-5p 抑制原代关节软骨细胞中循环菌株诱导的 ROS 产生和细胞凋亡。miR-100-5p 直接靶向 NOX4。过表达 NOX4 减弱了原代关节软骨细胞中 hucMSCs 衍生的外泌体介导的保护作用。环状菌株促进原代关节软骨细胞中 ROS 的产生和凋亡，而 hucMSCs 衍生的外泌体 miR-100-5p 通过其靶标 NOX4 消除了这种情况。这些发现强调了 miR-100-5p/NOX4 轴在原发性关节软骨细胞损伤中的重要性，并为关节软骨细胞损伤和骨关节炎的治疗策略提供了新的见解。过表达 NOX4 减弱了原代关节软骨细胞中 hucMSCs 衍生的外泌体介导的保护作用。环状菌株促进原代关节软骨细胞中 ROS 的产生和凋亡，而 hucMSCs 衍生的外泌体 miR-100-5p 通过其靶标 NOX4 消除了这种情况。这些发现强调了 miR-100-5p/NOX4 轴在原发性关节软骨细胞损伤中的重要性，并为关节软骨细胞损伤和骨关节炎的治疗策略提供了新的见解。过表达 NOX4 减弱了原代关节软骨细胞中 hucMSCs 衍生的外泌体介导的保护作用。环状菌株促进原代关节软骨细胞中 ROS 的产生和凋亡，而 hucMSCs 衍生的外泌体 miR-100-5p 通过其靶标 NOX4 消除了这种情况。这些发现强调了 miR-100-5p/NOX4 轴在原发性关节软骨细胞损伤中的重要性，并为关节软骨细胞损伤和骨关节炎的治疗策略提供了新的见解。