| 张怡文,潘春然,李霁云,等.适度运动训练通过抑制SHP2诱导的线粒体损伤改善骨关节炎进展.骨科,2025,16(6): 527-536. |
| 适度运动训练通过抑制SHP2诱导的线粒体损伤改善骨关节炎进展 |
| Moderate exercise training ameliorates osteoarthritis progression by suppressing SHP2-induced mitochondrial damage |
| 投稿时间：2025-10-08 |
| DOI：10.3969/j.issn.1674-8573.2025.06.009 |
| 中文关键词: 骨关节炎 运动训练 含Src同源2结构域蛋白酪氨酸磷酸酶2 线粒体损伤 |
| 英文关键词: Osteoarthritis Exercise training SH2 domain-containing tyrosine phosphatase 2 Mitochondrial damage |
| 基金项目:国家自然科学基金（82272610） |
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| 中文摘要: |
| 目的 探讨适度运动训练通过调节蛋白酪氨酸磷酸酶-2（SH2 domain-containing tyrosine phosphatase 2，SHP2）介导的线粒体功能损伤对骨关节炎（osteoarthritis，OA）进展的影响及其作用机制。方法 在细胞实验中，采用白细胞介素-1β（interleukin-1 beta，IL-1β）处理构建炎症软骨细胞模型，检测SHP2表达变化；分别通过过表达及siRNA质粒调控软骨细胞中SHP2的表达，以明确SHP2在OA进程中的作用；进一步利用细胞荧光染色分析SHP2参与OA病理过程的机制。在动物实验中，选取雄性SD大鼠，通过内侧半月板不稳定（destabilization of medial meniscus，DMM）手术建立OA模型，随后进行为期6周的适度运动训练（速度15 m/min，每日30 min，每周5天），评估适度运动对OA进展的改善作用。结果 炎性软骨细胞中磷酸化SHP2（phosphorylated SHP2，P-SHP2）蛋白水平显著升高，过表达SHP2导致软骨细胞合成代谢与分解代谢的失衡。而通过siRNA敲低SHP2能够缓解软骨细胞的炎症反应与软骨细胞线粒体损伤。适度运动训练能降低关节软骨中SHP2的表达进而改善大鼠关节软骨损伤。结论 适度运动训练通过抑制SHP2诱导的线粒体损伤改善OA进展。 |
| 英文摘要: |
| Objective To investigate the effects and mechanism of moderate exercise training on the progression of osteoarthritis (OA) by regulating SH2 domain-containing tyrosine phosphatase 2 (SHP2)-mediated mitochondrial dysfunction. Methods In cellular experiments, an inflammatory chondrocyte model was established using interleukin-1 beta (IL-1β) treatment, and changes in SHP2 expression were detected. Overexpression and siRNA interference techniques were applied to modulate SHP2 expression in chondrocytes, so as to clarify the role of SHP2 in OA progression. Furthermore, immunofluorescence staining was used to analyze the mechanism by which SHP2 participates in OA pathogenesis. In animal experiments, male SD rats were subjected to OA modeling via destabilization of the medial meniscus (DMM) surgery, followed by a 6-week moderate exercise training (15 m/min, 30 min/day, 5 days/week) to evaluate the ameliorative effect of moderate exercise on OA progression. Results The protein level of phosphorylated SHP2 (p-SHP2) was significantly elevated in inflammatory chondrocytes. Overexpression of SHP2 led to an imbalance between chondrocyte anabolism and catabolism. In contrast, knockdown of SHP2 by siRNA alleviated the inflammatory response and mitigated mitochondrial injury in chondrocytes. Moderate exercise training reduced SHP2 expression in articular cartilage and subsequently improved cartilage damage in rats. Conclusion Moderate exercise training ameliorates OA progression by suppressing SHP2-induced mitochondrial damage. |
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