Costunolide Inhibits Osteoclast Differentiation by Suppressing c-Fos Transcriptional Activity

被引：21

作者：

Cheon, Yoon-Hee ^{[1
]}

Song, Mi Jin ^{[1
]}

Kim, Ju-Young ^{[1
]}

Kwak, Seong Cheoul ^{[1
]}

Park, Ju Ha ^{[1
]}

Lee, Chang Hoon ^{[2
]}

Kim, Jeong Joong ^{[1
,4
]}

Kim, Jung Young ^{[1
]}

Choi, Min Kyu ^{[1
,4
,5
]}

Oh, Jaemin ^{[1
,4
]}

Kim, Youn-Chul ^{[6
]}

Yoon, Kwon-Ha ^{[3
]}

Kwak, Han Bok ^{[1
,4
]}

Lee, Myeung Su ^{[2
,4
]}

机构：

[1] Wonkwang Univ, Dept Anat, Iksan 570749, Jeonbuk, South Korea

[2] Wonkwang Univ, Dept Internal Med, Div Rheumatol, Iksan 570749, Jeonbuk, South Korea

[3] Wonkwang Univ, Sch Med, Iksan 570749, Jeonbuk, South Korea

[4] Wonkwang Univ, Inst Skeletal Dis, Iksan 570749, Jeonbuk, South Korea

[5] Wonkwang Univ, Inst Environm Sci, Iksan 570749, Jeonbuk, South Korea

[6] Wonkwang Univ, Coll Pharm, Standardized Mat Bank New Bot Drugs, Iksan 570749, Jeonbuk, South Korea

来源：

PHYTOTHERAPY RESEARCH | 2014年 / 28卷 / 04期

关键词：

sesquiterpene lactone; c-Fos; osteoclast; osteoporosis; costunolide; NUCLEAR-FACTOR; SESQUITERPENE LACTONES; GENE-EXPRESSION; ANTICANCER AGENTS; BONE-RESORPTION; CELLS; PARTHENOLIDE; ACTIVATION; NFATC1; RANKL;

D O I：

10.1002/ptr.5034

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant properties and mediates apoptosis. However, its effects and mechanism of action in osteoclasts remain unknown. Herein, we found that costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affecting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen-activated protein kinase and NF-kappa B pathways. However, costunolide suppressed nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression via inhibition of c-Fos transcriptional activity without affecting RANKL-induced c-Fos expression. The inhibitory effects of costunolide were rescued by overexpression of constitutively active (CA)-NFATc1. Taken together, our results suggest that costunolide inhibited RANKL-induced osteoclast differentiation by suppressing RANKL-mediated c-Fos transcriptional activity. Copyright (c) 2013 John Wiley & Sons, Ltd.

引用

页码：586 / 592

页数：7

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