Quercetin inhibits macrophage polarization through the p-38α/β signaling pathway and regulate OPG/RANKL balance in a mouse skull model
Quercetin inhibits macrophage polarization through the p-38α/β signaling pathway and regulate OPG/RANKL balance in a mouse skull model
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槲皮素通过 p-38α/β 信号通路抑制巨噬细胞极化并调节小鼠颅骨模型中的 OPG/RANKL 平衡
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发表时间：
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影响因子：
5.3
通讯作者：
Yuan-Qing Mao
中科院分区：
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作者：
Yu-Wei Ge;Kai Feng;Xiao-Liang Liu;Zhen-An Zhu;Hong-Fang Chen;Yong-Yun Chang;Zhen-Yu Sun;Hao-Wei Wang;Jing-Wei Zhang;De-Gang Yu;Yuan-Qing Mao
磨损颗粒引起的无菌性松动是人工全髋关节置换术后常见的并发症。我们研究了槲皮素对磨损颗粒介导的巨噬细胞极化、炎症反应和骨溶解的影响。在体外，我们通过流式细胞仪、免疫荧光分析和小干扰p-38α/β核糖核酸实验证实，钛颗粒通过p-38α/β信号通路促进RAW264.7细胞向M1巨噬细胞分化。我们用酶联免疫吸附试验证实，钛颗粒存在时，M1巨噬细胞的蛋白表达增加，这些促炎因子进一步调节OPG/RANKL的失衡，促进破骨细胞的分化。然而，这种作用可以被抑制，并且M2巨噬细胞的蛋白表达被Quercetin所增强。在体内，通过μ-CT、H&E染色、免疫组织化学和免疫荧光分析，我们在小鼠颅骨中发现了类似的结果。我们从溶骨性组织患者身上获取样本。免疫荧光分析表明，磨损颗粒周围的巨噬细胞大多为M1巨噬细胞，并释放了促炎因子。钛颗粒介导的M1巨噬细胞极化通过p-38RANKL信号通路引起促炎因子的释放，调节α/β/RANKL平衡。巨噬细胞极化有望成为临床药物治疗的新靶点。
Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle-mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p-38α/β signaling pathway by using flow cytometry, immunofluorescence assay and small interfering p-38α/β RNA. We used enzyme-linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro-inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ-CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro-inflammatory factors were released. Titanium particle-mediated M1 macrophage polarization, which caused the release of pro-inflammatory factors through the p-38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.