Tocotrienol regulates osteoclastogenesis in rheumatoid arthritis.

Tocotrienol regulates osteoclastogenesis in rheumatoid arthritis.
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DOI:
10.3904/kjim.2019.372
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发表时间:
2021-03
期刊:
The Korean journal of internal medicine
影响因子:
--
通讯作者:
Kim HR
Kim HR
中科院分区:
其他
文献类型:
--
作者:
Kim KW;Kim BM;Won JY;Min HK;Lee SJ;Lee SH;Kim HR

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本研究旨在探讨生育三烯醇是否调节类风湿关节炎(RA)中白细胞介素17 (IL-17)诱导的破骨细胞生成。我们利用RA成纤维细胞样滑膜细胞(FLS),结合实时聚合酶链反应和酶联免疫吸附试验,评估了生育三烯醇对il -17诱导的核因子κ B配体受体激活剂(RANKL)产生的影响。il -17处理的RA FLS和Th17细胞经生育三烯醇和单核细胞培养后证实有破骨细胞分化。我们用流式细胞术分析了生育三烯醇对外周血单核细胞Th17细胞百分比和Th17细胞因子水平的抑制作用。我们发现IL-17刺激FLS产生RANKL,而生育三烯醇降低了IL-17诱导的RANKL的产生。生育三烯醇降低il -17诱导的哺乳动物雷帕霉素靶蛋白、细胞外信号调节激酶和κ b - α抑制剂的激活。当单核细胞与IL-17、RANKL、IL-17处理的FLS或Th17细胞孵育时,破骨细胞分化,生育三烯醇抑制这种破骨细胞分化。生育三烯醇降低Th17细胞的分化和IL-17和sRANKL的产生;然而,生育三烯醇对Treg细胞分化没有影响。生育三烯醇抑制IL-17激活的RA FLS中RANKL的产生和IL-17激活的破骨细胞的形成。此外,生育三烯醇还能降低Th17的分化。因此,生育三烯醇可能是治疗类风湿性关节炎骨破坏过程的新选择。
The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.
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