西瑞香素通过NF-κB途径抑制RANKL诱导的破骨细胞分化  

Daphnoretin Inhibiting RANKL-induced Osteoclastogenesis by NF-κB Signaling Pathway

作　　者：缪利明 周佳瑛 林芝 黄溶 赵文君 施梦芸 王逸宁 陈子怡 郑绿珍 汪蕾 Miao Liming;Zhou Jiaying;Lin Zhi;Huang Rong;Zhao Wenjun;Shi Mengyun;Wang Yining;Chen Ziyi;Zheng Lvzhen;Wang Lei(l.Department of Brain Surgery,Hangzhou Ninth People's Hospital,Hangzhou 311200,China;Second Clinical Medical College of Wenzhou Medical University;First Clinical Medical College,School of Information and Engineering,Wenzhou Medical University;Department of Pathophysiology,School of Basic Medical Sciences,Wenzhou Medical University)

机构地区：[1]杭州市第九人民医院脑外科,杭州311200 [2]温州医科大学第二临床医学院 [3]温州医科大学第一临床医学院、信息与工程学院 [4]温州医科大学基础医学院病理生理学教研室

出　　处：《中国药师》2021年第8期477-481,共5页China Pharmacist

摘　　要：目的:研究西瑞香素作为一种具有抗炎抗氧化作用的中药成分对破骨细胞分化的影响及机制。方法:从BALB/c小鼠骨髓中分离获得骨髓单核细胞,使用GST-rRANKL诱导形成破骨细胞并分为3组:对照组、RANKL诱导组和RANKL+西瑞香素组,采用TRAcP染色评估西瑞香素对破骨细胞成熟与融合的影响,用Western Blot和qRT-PCR检测破骨细胞相关表型蛋白和核因子κB(NF-κB)信号通路蛋白,构建荧光素酶报告基因检测转录因子NF-κB活性。结果:西瑞香素能够显著抑制RANKL诱导的破骨细胞形成,抑制RANKL刺激后的Acp5、V-ATPase-d2和CTSK的转录水平,并抑制与破骨细胞分化密切相关的两个转录因子NFATc-1和c-Fos的表达量。西瑞香素能促进IκB-α的表达,从而抑制NF-κB活性。结论:西瑞香素通过促进IκB-α的表达,抑制NF-κB活性,使破骨细胞分化相关的关键转录因子NFATc-1和c-Fos的表达量下调,从而通过抑制NF-κB途径发挥抑制RANKL诱导的破骨细胞分化的作用。Objective:To determine the effect of daphnetin on osteoclast differentiation as a promising ant-inflammation natural compound.Methods:BMMs were isolated from BALB/c mice and then divided into 3 groups:control group,RANKL group and RANKL+daphnoretin group.TRAcP staining was applied to evaluate the effect of daphnoretin on maturation and fusion of osteoclasts.Western blot and qRT-PCR were utilized to assay the expressions of nuclear factor-κB(NF-κB)signaling and osteoclast-related proteins.Luciferase assay was used to detect the activity of NF-κB.Results:The results showed that daphnoretin could significantly inhibit the differentiation of osteoclasts and the transcription levels of Acp5,V-ATPase-d2 and CTSK after RANKL stimulation.Two significant transcription factors,NFATc-1 and c-Fos,were also inhibited.Daphnoretin promoted the expression of IκB-α,thereby inhibited the activity of NF-κB.Conclusion:Daphnoretin inhibits RANKL-induced osteoclastogenesis by enhancing the expression of IκB-α,thus inhibiting the activation of NF-κB resulting in the down-regulation of NFATc-1 and c-Fos,two vital osteoclastogenesis-related transcription factors.Through the inhibition of NF-κB signaling pathway,daphnoretin may exert its anti-osteoclastogenesis effect after RANKL stimulation.

关 键 词：西瑞香素 破骨细胞 核因子ΚB 核因子ΚB受体活化因子配体 

分 类 号：R965.1[医药卫生—药理学]