Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-κB activation and titanium particle-induced osteolysis in a mouse model

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:399

Article

Huang, Jianbin¹  Zhou, Lin²  Wu, Huafei^2,3  Pavlos, Nathan³  Chim, Shek Man²  Liu, Qian^2,4  Zhao, Jinmin⁴  Xue, Wei⁵  Tan, Ren Xiang⁶  Ye, Jiming^7,8  Xu, Jun⁹  Ang, Estabelle S.¹⁰  Feng, Haotian^2,11  Tickner, Jennifer²  Xu, Jiake²  Ding, Yue¹ 

[1] Sun Yat Sen Univ, Mem Hosp, Dept Orthopaed, Guangzhou 510275, Guangdong, Peoples R China

[2] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia

[3] Univ Western Australia, Sch Surg, Ctr Orthopaed Res, Perth, WA 6009, Australia

[4] Guangxi Med Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Res Ctr Regenerat Med, Guangxi 530021, Peoples R China

[5] Jinan Univ, Dept Biomed Engn, Guangdong Higher Educ Inst, Key Lab Biomat, Guangzhou 510632, Guangdong, Peoples R China

[6] Nanjing Univ, Sch Med, Inst Funct Biomol, Nanjing 210093, Jiangsu, Peoples R China

[7] RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic 3083, Australia

[8] RMIT Univ, Sch Hlth Sci, Melbourne, Vic 3083, Australia

[9] Sun Yat Sen Univ, Sch Pharmaceut Sci, Res Ctr Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China

[10] Univ Western Australia, Sch Dent, Perth, WA 6009, Australia

[11] Nestle R&D China Ltd, Program Nutr & Bone & Joint Hlth, Beijing 100095, Peoples R China

关键词: Triptolide;    Osteoclastogenesis;    RANKL;    NF-kappa B;    Osteolysis;    Titanium particle;   

DOI  :  10.1016/j.mce.2014.10.016

来源: Elsevier

【 摘 要 】

The RANKL-induced NF-kappa B signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-kappa B activation using a luciferase reporter gene assay in RAW264.7 cells, we identified triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-kappa B activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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