Department of Molecular Medicine, Histology Unit, University of Padova, 35121 Padova, Italy.
Musculoskeletal Pathology and Oncology Laboratory, Orthopedic Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.
Cells. 2020 May 26;9(6):1328. doi: 10.3390/cells9061328.
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.
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.
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.
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.
骨关节炎（OA）的发展和进展与巨噬细胞介导的炎症有关，这种炎症会产生广泛的细胞因子和活性氧物质（ROS）。本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）与乳糖修饰壳聚糖（CTL）联合使用对促炎分子和金属蛋白酶（MMPs）表达的影响。
为了评估软骨细胞对 HA 和 CTL 在巨噬细胞来源的炎症介质存在下的反应，将细胞暴露于激活单核细胞 U937 的条件培养基（CM）中，并分析细胞活力、促炎介质和 MMPs 表达或 ROS 生成的变化。
CTL 诱导的软骨细胞活力变化在 HA 存在的情况下减少。激活的 U937 单核细胞（巨噬细胞）的 CM 显著增加了人软骨细胞培养物中促炎分子和 MMPs 的基因表达以及细胞内 ROS 的产生。HA、CTL 及其组合减轻了氧化损伤，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。
本研究表明，HA-CTL 混合物可减轻巨噬细胞诱导的炎症，抑制 MMPs 的表达，并具有抗氧化作用。这一证据为开发早期 OA 治疗方法提供了初步步骤。
