Department of Orthopaedics, Quzhou Traditional Chinese Medicine Hospital at the Junction of Four Provinces Affiliated to Zhejiang Chinese Medical University, Quzhou, Zhejiang, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
PLoS One. 2024 Aug 22;19(8):e0301199. doi: 10.1371/journal.pone.0301199. eCollection 2024.
Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns and macrophages play a crucial role. However, the interaction of these mediators, the exact cause, and the treatment of knee osteoarthritis (KOA) are still unclear. Moreover, the interaction of interleukin (IL)-33, platelet-derived growth factor-BB (PDGF-BB), and matrix metalloproteinase-9 (MMP-9) with other factors in the pathogenesis of KOA has not been elaborately explored.
Therefore, in this study, we analyzed the expression of IL-33, PDGF-BB, and MMP-9 in the knee cartilage tissue of model mice, murine KOA was induced by using the destabilization of the medial meniscus (DMM) model.
Compared with the sham operation control group, the expression levels of PDGF-BB, IL-33, and MMP-9 were increased significantly, and the pathological sections showed obvious cartilage damage. Additionally, we assessed the levels of IL-33 and MMP-9 expression in the knee joint of KOA model mice following intervention with PDGF-BB antibody, and we found that the expression level of MMP-9 was reduced following intervention with IL-33 antibody. When the effects of the three antibodies were compared in a mouse disease model, it was discovered that the IL-33 antibody could dramatically lower the relative expression level of MMP-9, resulting in the least amount of cartilage damage and improved protection. In conclusion, inhibiting IL-33 can significantly lower inflammatory factor levels in the knee joint, including IL-33 and MMP-9, and it can improve cartilage breakdown in osteoarthritis of the knee.
Overall, the results indicate that IL-33 has a therapeutic function in the treatment of knee osteoarthritis and may be a novel target for treatment of the underlying causes of KOA. Additionally, PDGF-BB might be an upstream pathway of IL-33, and KOA's MMP-9 is an downstream pathway of IL-33.
骨关节炎（OA）是一种慢性炎症性疾病，其中促炎细胞因子、损伤相关分子模式和巨噬细胞起着至关重要的作用。然而，这些介质的相互作用、确切的原因以及膝骨关节炎（KOA）的治疗仍不清楚。此外，白细胞介素（IL）-33、血小板衍生生长因子-BB（PDGF-BB）和基质金属蛋白酶-9（MMP-9）与 KOA 发病机制中的其他因素的相互作用尚未详细探讨。
因此，在这项研究中，我们分析了模型小鼠膝关节软骨组织中 IL-33、PDGF-BB 和 MMP-9 的表达，使用内侧半月板不稳定（DMM）模型诱导鼠 KOA。
与假手术对照组相比，PDGF-BB、IL-33 和 MMP-9 的表达水平显著升高，病理切片显示明显的软骨损伤。此外，我们评估了 PDGF-BB 抗体干预后 KOA 模型小鼠膝关节中 IL-33 和 MMP-9 表达水平，发现 IL-33 抗体干预后 MMP-9 表达水平降低。在小鼠疾病模型中比较三种抗体的作用时，发现 IL-33 抗体可显著降低 MMP-9 的相对表达水平，导致软骨损伤最小，保护作用改善。总之，抑制 IL-33 可显著降低膝关节中炎症因子的水平，包括 IL-33 和 MMP-9，并可改善膝骨关节炎的软骨破坏。
总的来说，结果表明 IL-33 在治疗膝骨关节炎方面具有治疗作用，可能是治疗 KOA 根本原因的新靶点。此外，PDGF-BB 可能是 IL-33 的上游途径，而 KOA 的 MMP-9 是 IL-33 的下游途径。
