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| IL-37联合机械应力改善创伤性骨关节炎的作用研究 |
| The therapeutic effect of IL-37 combined with mechanical stress on post-traumatic osteoarthritis |
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| DOI：10.3969/j.issn.1006-7108.2026.09.006 |
| 中文关键词: 创伤性骨关节炎 软骨细胞 软骨 IL-37 机械应力 |
| 英文关键词:post-traumatic osteoarthritis chondrocyte cartilage IL-37 mechanical stress |
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| 中文摘要: |
| 目的 探讨IL-37（interleukin-37，IL-37）联合机械应力对小鼠创伤性骨关节炎（post-traumatic osteoarthritis，PTOA）软骨损伤的修复作用。方法 构建原代小鼠软骨细胞白介素-1β（interleukin-1β，IL-1β）炎症模型，给予不同浓度IL-37重组蛋白干预并联合机械牵张刺激，检测炎症、分解及合成相关指标变化；构建Human-IL-37b基因敲入小鼠模型，以内侧半月板失稳术（destabilization of the medial meniscus，DMM）建立PTOA模型并开展4周跑台运动，检测血清炎症因子、软骨形态钙化及相关基因蛋白表达。结果IL-37可显著抑制IL-1β诱导的软骨细胞炎症反应，下调肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、血小板反应蛋白解整合素金属肽酶5（a disintegrin and metalloproteinase with thrombospondin5，ADAMTS-5）表达、上调Ⅱ型胶原蛋白（Collagen-Ⅱ）表达；IL-37与机械牵张均可减轻炎症环境下软骨细胞凋亡，联合干预对炎症及分解因子的抑制作用更强；Human-IL-37b基因敲入可降低PTOA小鼠血清中IL-1β和TNF-α水平，改善软骨形态及钙化，下调软骨组织IL-1β、TNF-α、ADAMTS-5、基质金属蛋白酶9（matrix metalloproteinase 9，MMP-9），上调 Collagen-Ⅱ的表达；运动干预亦具有软骨保护作用，且联合干预的效果优于单纯运动。结论 IL-37可缓解软骨细胞炎症反应并减轻PTOA软骨损伤，机械应力干预亦具有保护效应；二者联合可增强抗炎、抑分解及促合成作用，有望成为PTOA防治新策略。 |
| 英文摘要: |
| Objective To investigate the repair effect of IL-37 combined with mechanical stress on cartilage damage in mice with post-traumatic osteoarthritis (PTOA). Methods A primary mouse chondrocyte inflammation model was established using IL-1β stimulation. Cells were treated with different concentrations of recombinant IL-37 protein alone or in combination with mechanical stretch stimulation. Changes in inflammatory, catabolic, and anabolic markers were detected. A human-IL-37b knock-in mouse model was constructed. PTOA was induced via destabilization of the medial meniscus (DMM) surgery. Mice then underwent 4 weeks of treadmill exercise. Serum inflammatory factors, cartilage morphology and calcification, and the expressions of related genes and proteins were assessed. Results IL-37 significantly inhibited IL-1β-induced inflammatory responses in chondrocytes, down-regulated the expressions of TNF-α and ADAMTS-5, and up-regulated collagen-Ⅱ expression. Both IL-37 and mechanical stretch reduced chondrocyte apoptosis under inflammatory conditions. Combined intervention exerted a stronger inhibitory effect on inflammatory and catabolic factors. Human-IL-37b knock-in reduced serum levels of IL-1β and TNF-α in PTOA mice, improved cartilage morphology and calcification, down-regulated the expressions of IL-1β, TNF-α, ADAMTS-5, and MMP-9 in cartilage tissue, and up-regulated collagen-Ⅱ expression. Exercise intervention also exhibited chondroprotective effects. The combined intervention was superior to exercise alone. Conclusion IL-37 alleviates chondrocyte inflammatory responses and reduces cartilage damage in PTOA. Mechanical stress intervention also exerts protective effects. The combination of the two enhances anti-inflammatory, anti-catabolic, and pro-anabolic effects, which is expected to become a new strategy for the prevention and treatment of PTOA. |
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