Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages
Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages
复制标题
黄芪甲苷 IV 通过复极促炎巨噬细胞的表型来改善类固醇诱导的股骨头坏死
DOI：
10.1016/j.intimp.2020.107345
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发表时间：
2021-03-08
影响因子：
5.6
通讯作者：
Yu, Xiaowei
中科院分区：
文献类型：
--
作者：
Jiang, Chaolai;Zhou, Zubin;Yu, Xiaowei
股骨头坏死（ON-FH）是使用类固醇的常见并发症。促炎性巨噬细胞在骨细胞凋亡中起着至关重要的作用。本研究的目的是评价植物提取物黄芪甲苷IV（AS-IV）治疗ON-FN。骨髓源性巨噬细胞（BMDMs）处理脂多糖（LPS），IFN-？或IL-4诱导M1和M2样表型。采用实时荧光定量PCR和Western blot检测M1和M2的表型标记。流式细胞仪检测细胞表面MHC Ⅱ、CD 206、F4/80、CD 11b水平及细胞凋亡情况。用糖皮质激素诱导小鼠ON-FN。TNF-？采用酶联免疫吸附法测定股骨头中IL-113的含量。AS-IV使巨噬细胞从M1表型复极化为M2表型。与未处理的M1巨噬细胞相比，AS-IV处理的M1巨噬细胞的培养基诱导较少的细胞凋亡骨细胞。在ON-FH小鼠，M1巨噬细胞的比例下降，股骨头AS-IV，伴随着TNF-？IL-113水平。AS-IV通过其使巨噬细胞从M1样表型复极化为M2样表型、促进骨细胞存活、减轻关节炎症状和减少炎性细胞因子的作用而有效缓解ON-FH。
Osteonecrosis of the femoral head (ON-FH) is a common complication of steroid use. Pro-inflammatory macrophages play a crucial role in the apoptosis of osteocytes. The objective of the study was to evaluate a plant extract astragaloside IV (AS-IV) in treating ON-FN. Bone-marrow-derived macrophages (BMDMs) were treated with lipopolysaccharides (LPS), IFN-? or IL-4 to induce M1 and M2-like phenotypes. Quantitative real-time PCR and Western blot were used to examine M1 and M2 phenotypic markers. Flow cytometry was used to analyze MHC II, CD206, F4/80, and CD11b levels and cell apoptosis. Glucocorticoid was used to induce ON-FN in mice. TNF-? and IL-113 levels in femoral head were determined using enzyme-linked immunosorbent assay. AS-IV repolarized macrophages from M1 to M2 phenotypes. Culture medium from AS-IV treated M1 macrophages induced less cell apoptosis osteocytes compared to that from untreated M1 macrophages. In ON-FH mice, the ratio of M1 macrophages was decreased in the femoral head by AS-IV, concomitant with a decrease in TNF-? and IL-113 levels. AS-IV is effective in alleviating ON-FH through its effects in repolarizing macrophages from M1-like phenotype to M2-like phenotype, promoting survival of osteocytes, reducing arthritic symptoms, and decreasing inflammatory cytokines.