Arthritis Rheumatol:抑制IL-17A可减轻脊柱关节炎的炎症和新骨形成

2018-11-05 xiangting MedSci原创

预防性和治疗性抑制IL-17A均可减少HLA-B27/Huβ2m转基因大鼠的炎症以及新骨形成。

脊柱关节炎(SpA)中炎症和新骨形成是否相结合,以及如何结合目前尚不清楚。这项研究评估了IL-17A是这两个过程关键驱动因素的假说。

使用地塞米松、β-糖磷酸酶和抗坏血酸分化的SpA成纤维细胞样滑膜细胞(FLS),在成骨细胞分化测定中测试TNF和IL-17A对骨生成的影响。在预防和治疗的情况下,在脊柱关节炎模型、HLA-B27/Huβ2m转基因大鼠中进行IL-17A阻断。通过显微CT成像、组织学和基因表达谱评估炎症和新骨形成。

TNF和IL-17A显著增加体外成骨细胞的分化。在体内,IL-17A的预防性阻断可显著延缓脊柱炎和关节炎的发展,降低关节炎的严重程度。这与预防骨质流失和骨膜新骨形成相关。在最初的炎性损伤后,靶向IL-17A的治疗也显著减少中轴型和外周关节炎症。这再次与脊柱和外周结构损伤的显著减少相关,其中包括新骨形成。靶组织的RNA测序证实IL-17A是该模型中疾病分子标记的关键驱动因素,并且治疗性的抗IL17A治疗逆转了炎症特征,也抑制了骨损伤相关选定基因表达。

预防性和治疗性抑制IL-17A均可减少HLA-B27/Huβ2m转基因大鼠的炎症以及新骨形成。结合IL-17A促进人SpA FLS成骨细胞分化的能力,这些数据表明IL-17A驱动的炎症与SpA中病理性新骨形成之间存在直接关联。

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    2018-11-07 lmm397
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    2018-11-07 zhaojie88
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    2018-11-07 fzwish20000
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    2018-11-07 jjjiang0202

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