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Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway

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收录情况： ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：重点期刊

作者：
Zeng, Xiang-zhou[1,2,3] * ; Zhang, Yue-yang[1,2] * ; Yang, Qin[1,2] ; Wang, Song[4] ; Zou, Bin-hua[1,2] ; Tan, Yan-hui[1,2] ; Zou, Min[2] ; Liu, Shu-wen[2] ; Li, Xiao-juan[1,2] ;
机构： [1]Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China [3]Department ofPharmacology, Hainan Medical College, Haikou 571199, China [4]Department of Surgery, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China
出处：
DOI： 10.1038/s41401-019-0289-6
ISSN：

关键词： artesunate osteoclast LPS PP2B-A alpha Ca2+ NFATc1 TLR4 RAW264 7 cells chronic infectious diseases

摘要：
In chronic infectious diseases caused by gram-negative bacteria, such as osteomyelitis, septic arthritis, and periodontitis, osteoclastic activity is enhanced with elevated inflammation, which disturbs the bone homeostasis and results in osteolysis. Lipopolysaccharide (LPS), as a bacteria product, plays an important role in this process. Recent evidence shows that an antimalarial drug artesunate attenuates LPS-induced osteolysis independent of RANKL. In this study we evaluated the effects of artesunate on LPS-induced osteoclastogenesis in vitro and femur osteolysis in vivo, and explored the mechanisms underlying the effects of artesunate on LPS-induced osteoclast differentiation independent of RANKL. In preosteoclastic RAW264.7 cells, we found that artesunate (1.56-12.5 mu M) dose dependently inhibited LPS-induced osteoclast formation accompanied by suppressing LPS-stimulated osteoclast-related gene expression (Fra-2, TRAP, Cathepsin K, beta 3-integrin, DC-STAMP, and Atp6v0d2). We showed that artesunate (3.125-12.5 mu M) inhibited LPS-stimulated nuclear factor of activated T cells c1 (NFATc1) but not NF-kappa B transcriptional activity; artesunate (6.25, 12.5 mu M) significantly inhibited LPS-stimulated NFATc1 protein expression. Furthermore, artesunate treatment markedly suppressed LPS-induced Ca2+ influx, and decreased the expression of PP2B-A alpha (calcineurin) and pPLC gamma 1 in the cells. In addition, artesunate treatment significantly decreased the expression of upstream signals TLR4 and TRAF6 during LPS-induced osteoclastogenesis. Administration of artesunate (10 mg/kg, ip) for 8 days effectively inhibited serum TNF-alpha levels and ameliorated LPS (5 mg/kg, ip)-induced inflammatory bone loss in vivo. Taken together, artesunate attenuates LPS-induced inflammatory osteoclastogenesis by inhibiting the expression of TLR4/TRAF6 and the downstream PLC gamma 1-Ca2+-NFATc1 signaling pathway. Artesunate is a valuable choice to treat bone loss induced by gram-negative bacteria infection or inflammation in RANKL-independent pathway.

基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81773740, 81073119, 81611130078]; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2015A030313287]; Natural Science Foundation of Hainan Province, China [817129]

基金编号： 81773740 81073119 81611130078 2015A030313287 817129

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外文
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中科院(CAS)分区：
出版当年[2019]版：
大类 | 2 区 医学
小类 | 2 区 化学综合 2 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 1 区 药学 2 区 化学：综合
JCR分区：
出版当年[2018]版：
Q1 PHARMACOLOGY & PHARMACY Q2 CHEMISTRY, MULTIDISCIPLINARY
最新[2023]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者机构： [1]Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China [3]Department ofPharmacology, Hainan Medical College, Haikou 571199, China
共同第一作者：
通讯作者：
通讯机构： [1]Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
推荐引用方式(GB/T 7714)：
Zeng Xiang-zhou,Zhang Yue-yang,Yang Qin,et al.Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway[J].ACTA PHARMACOLOGICA SINICA.2020,41(2):229-236.doi:10.1038/s41401-019-0289-6.
APA：
Zeng, Xiang-zhou,Zhang, Yue-yang,Yang, Qin,Wang, Song,Zou, Bin-hua...&Li, Xiao-juan.(2020).Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway.ACTA PHARMACOLOGICA SINICA,41,(2)
MLA：
Zeng, Xiang-zhou,et al."Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway".ACTA PHARMACOLOGICA SINICA 41..2(2020):229-236

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