Celastrol attenuates bone erosion in collagen-Induced arthritis mice and inhibits osteoclast differentiation and function in RANKL-induced RAW264.7

被引:96
作者
Gan, Ke [1 ,2 ]
Xu, Lingxiao [1 ]
Feng, Xiaoke [3 ]
Zhang, Qiande [3 ]
Wang, Fang [4 ]
Zhang, Miaojia [1 ]
Tan, Wenfeng [1 ]
机构
[1] Nanjing Med Univ, Dept Rheumatol, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Tradit Chinese Med, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Integrat Med Inst, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiol, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Celastrol; Osteodast; Collagen-Induced arthritis; WILFORDII HOOK-F; RHEUMATOID-ARTHRITIS; T-CELLS; AUTOIMMUNE ARTHRITIS; DOUBLE-BLIND; PATHOGENESIS; INFLAMMATION; MECHANISMS; EXTRACT; DAMAGE;
D O I
10.1016/j.intimp.2014.12.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Recently, the traditional Chinese medicine Tripterygium wilfordii Hook f (TwHF) of the Celastraceae family has attracted increasing attention for its potential therapeutic application in patients with rheumatoid arthritis (RA). It is well accepted that TwHF exerts the antirheumatic activity and mainly depends on its potent anti-inflammatory property. To further explore the therapeutic potential of the well-defined TwHF-derived single compound celastrol in RA, we study the therapeutic efficacy of celastrol on bone erosion in collagen-induced arthritis (CIA) mice and delineate its effects on osteodast differentiation and functions in RANKL-induced osteodast precursors RAW264.7 cell line. In CIA mice, daily injection of celastrol (beginning on day 28 after arthritis induction) markedly suppressed arthritis, and reduced bone damage in the joints as demonstrated by histology and bone micro-computed tomography (Cr). The effects were accompanied by reductions of osteoclast cells in joints, serum tartrate-resistant acid phosphatase (TRAP) 5b, and expression of osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcriptional factors (c-Fos, c-Jun and NFATc1). When RAW264.7 cells were treated with RANKL, celastrol inhibited the formation of TRAP + multinucleated cells and the bone-resorbing activity in dose-dependent manners. Furthermore, celastrol reduced the RANKL-induced expression of osteodastic genes and transcriptional factors, as well as phosphorylation of NF-kB and mitogen-activated protein kinases (MAPK). These findings show that celastrol could directly inhibit osteodast formation and function, suggesting a novel therapeutic strategy of celastrol for managing RA, especially in preventing bone destruction. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:239 / 246
页数:8
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