Background

Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF).

Results

DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats’ joints on the seventh day (inflammatory phase).

Conclusions

Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.

中文翻译：

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关节内富马酸单甲酯作为巨噬细胞极化治疗骨关节炎的前景疗法

背景

骨关节炎 (OA) 是一种慢性疾病，可能导致关节结构退化、软骨破坏、骨赘形成、软骨下骨破坏和疼痛。在这种情况下，促炎性巨噬细胞 1 型 (M1) 的比例高于抗炎性巨噬细胞 2 型 (M2) 的比例，可以作为 OA 进展的标志。这两种巨噬细胞类型之间的平衡成为 OA 的新治疗靶点。本研究旨在评估全身富马酸二甲酯（DMF）或局部关节内富马酸单甲酯（MMF）治疗实验性骨关节炎（EOA）的镇痛和巨噬细胞特征。

结果

通过灌胃的 DMF 或通过关节内注射的 MMF 在 EOA 大鼠的右膝中显示出步态参数的改善以及通过采用电子 von Frey 治疗的第 21 天（长期持续阶段）的机械阈值评估的伤害性恢复。DMF 处理在第五天（炎症阶段）减少了浸渍胶囊中的促炎性 TNF-α，同时增加了抗炎性 IL-10 细胞因子。MMF 治疗显示关节囊 mRNA 提取下调 iNOS 和 TNF-α 基因表达，同时上调 IL-10 和 MCP-1。然而，第七天（炎症期）CD206 并不显着，但高于未治疗的 EOA 大鼠关节。

结论

我们对 MIA 诱导的 EOA 模型的研究提出了基于巨噬细胞极化作为治疗靶点的人类 OA 治疗的新视角，根据系统性 DMF 或 MMF 局部治疗将促炎谱 M1 转变为抗炎谱 M2。 OA 严重程度。