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

BMC Complementary and Alternative Medicine

Dongyi He³  Jianping Zuo¹  Mengru Guo²  Shijun He¹  Rongsheng Wang³  Ting Jiang³  Yi Shen³ 

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

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

Others  :  1178850
DOI  :  10.1186/s12906-015-0566-y

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

【 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 κ-B ligand (RANKL)/receptor activator of nuclear factor κ-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) 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.

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-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.

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.

【 授权许可】

   
2015 Shen et al.; licensee BioMed Central.

【 图 表 】

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