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(5R)-5-Hydroxytriptolide (LLDT-8) inhibits osteoclastogenesis via RANKL/RANK/OPG signaling pathway

文献类型：期刊论文

作者Shen, Yi1,2; Jiang, Ting1,2; Wang, Rongsheng1,2; He, Shijun3; Guo, Mengru1,2; Zuo, Jianping3; He, Dongyi1,2
刊名BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
出版日期2015-03-24
卷号15
ISSN号1472-6882
关键词(5R)-5-Hydroxytriptolide Osteoclastogenesis Osteoprotegerin RANKL Rheumatoid arthritis
DOI10.1186/s12906-015-0566-y
文献子类Article
英文摘要Background: The aim of this study was to investigate the regulative activity of (5R)-5-hydroxytriptolide (LLDT-8) on receptor activator of nuclear factor kappa-B ligand (RANKL)/receptor activator of nuclear factor kappa-B (RANK)/Osteoprotegerin (OPG) system in rheumatoid arthritis (RA) and its anti-osteoclastogenesis mechanism. Methods: The expression of OPG, RANK and RANKL in CD3(+) T leukomonocytes in both peripheral blood and synovial fluid of RA patients was evaluated by flow cytometry. The levels of interleukin (IL) 1 beta, IL-6, IL-10, IL-21 and IL-23 in the supernatants of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were assayed by ELISA. Tartaric acid phosphatase (TRAP) staining was used to identify the osteoclast-like cells derived from RAW264.7. Western blotting analysis was used to check the downstream molecules of RANKL. Results: LLDT-8 increased the rate of OPG expression in CD3+ T leukomonocytes in peripheral blood as well as the ratio of OPG/RANKL in both peripheral blood and synovial fluid. LLDT-8 inhibited IL-1 beta, IL-6, IL-21 and IL-23 secretion, but promoted the secretion of IL-10 in the supernatants of PBMCs and SFMCs. In addition, LLDT-8 decreased the number of TRAP-positive cells derived from RAW264.7 in the presence of RANKL and M-CSF. Furthermore, LLDT-8 also inhibited the expression of p-I kappa B, a key regulator of RANKL signaling pathway. Conclusions: LLDT-8 exerts its anti-osteoclastogenesis effect in RA probably through regulating RANKL/RANK/OPG system and its downstream signaling pathway as well as cytokine productions.
WOS关键词COLLAGEN-INDUCED ARTHRITIS ; RHEUMATOID-ARTHRITIS ; DIFFERENTIATION ; VALIDATION ; EXPRESSION ; CYTOKINE ; MICE
资助项目Key projects of Shanghai Municipal Health Bureau[20114027] ; National Natural Science Funds of China[81273979]
WOS研究方向Integrative & Complementary Medicine
语种英语
出版者BIOMED CENTRAL LTD
WOS记录号WOS:000351899100001
源URL[http://119.78.100.183/handle/2S10ELR8/276600]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Zuo, Jianping
作者单位1.Shanghai Guanghua Hosp Integrated Tradit & Wester, Dept Rheumatol, Shanghai 200052, Peoples R China;
2.Shanghai Chinese Med Res Inst, Arthrit Inst integrated Tradit & Western Med, Shanghai 200052, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Shen, Yi,Jiang, Ting,Wang, Rongsheng,et al. (5R)-5-Hydroxytriptolide (LLDT-8) inhibits osteoclastogenesis via RANKL/RANK/OPG signaling pathway[J]. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,2015,15.
APA Shen, Yi.,Jiang, Ting.,Wang, Rongsheng.,He, Shijun.,Guo, Mengru.,...&He, Dongyi.(2015).(5R)-5-Hydroxytriptolide (LLDT-8) inhibits osteoclastogenesis via RANKL/RANK/OPG signaling pathway.BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,15.
MLA Shen, Yi,et al."(5R)-5-Hydroxytriptolide (LLDT-8) inhibits osteoclastogenesis via RANKL/RANK/OPG signaling pathway".BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 15(2015).

入库方式： OAI收割

来源：上海药物研究所

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