The development and progression of osteoarthritis (OA) is associated with macrophage-mediated inflammation that generates a broad spectrum of cytokines and reactive oxygen species (ROS). This study investigates the effects of mid-MW hyaluronic acid (HA) in combination with a lactose-modified chitosan (CTL), on pro-inflammatory molecules and metalloproteinases (MMPs) expression, using an in vitro model of macrophage-mediated inflammation. Methods. To assess chondrocyte response to HA and CTL in the presence of macrophage derived inflammatory mediators, cells were exposed to the conditioned medium (CM) of U937 activated monocytes and changes in cell viability, pro-inflammatory mediators and MMPs expression or ROS generation were analysed. Results. CTL induced changes in chondrocyte viability that are reduced by the presence of HA. The CM of activated U937 monocytes (macrophages) significantly increased gene expression of pro-inflammatory molecules and MMPs and intracellular ROS generation in human chondrocyte cultures. HA, CTL and their combinations counteracted the oxidative damage and restored gene transcription for IL-1β, TNF-α, Gal-1, MMP-3 and MMP-13 to near baseline values. Conclusions. This study suggests that HA-CTL mixture attenuated macrophage-induced inflammation, inhibited MMPs expression and exhibited anti-oxidative effects. This evidence provides an initial step toward the development of an early stage OA therapeutic treatment

中文翻译：

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乳糖修饰的壳聚糖和透明质酸混合物在体外巨噬细胞介导的炎症性骨关节炎模型中的抗炎性能。

骨关节炎（OA）的发展和进展与巨噬细胞介导的炎症有关，后者会产生广泛的细胞因子和活性氧（ROS）。这项研究使用巨噬细胞介导的炎症体外模型研究了中分子量透明质酸（HA）与乳糖修饰的壳聚糖（CTL）结合对促炎分子和金属蛋白酶（MMPs）表达的影响。方法。为了评估在巨噬细胞衍生的炎性介质存在下软骨细胞对HA和CTL的反应，将细胞暴露于U937激活的单核细胞的条件培养基（CM）中，并分析细胞活力，促炎性介质和MMPs表达或ROS生成的变化。结果。CTL诱导的软骨细胞活力变化被HA的存在减少了。活化的U937单核细胞（巨噬细胞）的CM显着增加了人类软骨细胞培养物中促炎分子和MMP的基因表达以及细胞内ROS的产生。HA，CTL及其组合抵消了氧化损伤，并将IL-1β，TNF-α，Gal-1，MMP-3和MMP-13的基因转录恢复到接近基线值。结论。这项研究表明，HA-CTL混合物可减轻巨噬细胞诱导的炎症，抑制MMPs表达并表现出抗氧化作用。该证据为开发早期OA治疗提供了第一步 CTL及其组合抵消了IL-1β，TNF-α，Gal-1，MMP-3和MMP-13的氧化损伤并将基因转录恢复到接近基线值。结论。这项研究表明，HA-CTL混合物可减轻巨噬细胞诱导的炎症，抑制MMPs表达并表现出抗氧化作用。该证据为开发早期OA治疗提供了第一步 CTL及其组合抵消了氧化损伤，并将IL-1β，TNF-α，Gal-1，MMP-3和MMP-13的基因转录恢复到接近基线值。结论。这项研究表明，HA-CTL混合物可减轻巨噬细胞诱导的炎症，抑制MMPs表达并表现出抗氧化作用。该证据为开发早期OA治疗提供了第一步