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

BMC Complementary and Alternative Medicine

Research Article

Mengru Guo¹  Ting Jiang¹  Yi Shen¹  Rongsheng Wang¹  Dongyi He¹  Jianping Zuo²  Shijun He² 

[1] Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, 200052, Shanghai, China;Arthritis Institute of integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, 200052, Shanghai, China;Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China;

关键词: (5R)-5-Hydroxytriptolide;    Osteoclastogenesis;    Osteoprotegerin;    RANKL;    Rheumatoid arthritis;   

DOI  :  10.1186/s12906-015-0566-y

 received in 2014-08-22, accepted in 2015-02-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe aim of this study was to investigate the regulative activity of (5R)-5-hydroxytriptolide (LLDT-8) on receptor activator of nuclear factor κ-B ligand (RANKL)/receptor activator of nuclear factor κ-B (RANK)/Osteoprotegerin (OPG) system in rheumatoid arthritis (RA) and its anti-osteoclastogenesis mechanism.MethodsThe 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) 1β, 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.ResultsLLDT-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-1β, 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-IκB, a key regulator of RANKL signaling pathway.ConclusionsLLDT-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.

【 授权许可】

Unknown   
© Shen et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.