Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation

被引：21

作者：

Kong, Xiangying ^{[1
]}

Wu, Wenbin ^{[1
]}

Yang, Yue ^{[1
]}

Wan, Hongye ^{[1
]}

Li, Xiaomin ^{[1
]}

Zhong, Michun ^{[1
]}

Zhao, Hongyan ^{[2
]}

Su, Xiaohui ^{[1
]}

Jia, Shiwei ^{[3
]}

Ju, Dahong ^{[2
]}

Lin, Na ^{[1
]}

机构：

[1] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

[2] China Acad Chinese Med Sci, Inst Basic Theory, Beijing 100700, Peoples R China

[3] Guangzhou Kanghe Pharmaceut Ltd Co, Guangzhou 511440, Guangdong, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2015年 / 13卷

关键词：

Anemone flaccida; RANKL; Osteoclasts; Bone resorption; MAPKs; NF-kappa B; IN-VITRO; OSTEOPROTEGERIN LIGAND; RHEUMATOID-ARTHRITIS; PATHWAYS; INDUCTION; HOMEOSTASIS; CELLS; VIVO;

D O I：

10.1186/s12967-015-0440-1

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as rheumatoid arthritis and osteoporosis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against bone destructive diseases. In the present study, we investigated the effects of total saponin (TS) from Anemone flaccida Fr. Schmidt, on receptor activator of nuclear factor-kappa B ligand ( RANKL)-induced in vitro osteoclast differentiation. We observed that TS concentration-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 cell and bone marrow-derived macrophages (BMMs), as well as decreased extent of actin ring formation and lacunar resorption. The RANKL-stimulated expression of osteoclast-related transcription factors were also diminished by TS. Moreover, TS blocked the RANKL-triggered TRAF6 expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and I kappa B-alpha, and inhibited NF-kappa B p65 DNA binding activity. Furthermore, TS almost abrogated the nuclear factor of activated T cells (NFATc1) and c-Fos expression. Taken together, our results demonstrated that TS suppresses RANKL-induced osteoclast differentiation and inflammatory bone loss via the down-regulation of TRAF6 level, suppression of JNK and p38 MAPKs and NF-kappa B activation, and subsequent decreased expression of c-Fos and NFATc1. Therefore, TS may be a potential agent and needs to be more evaluated in vivo or in clinical trials to become a therapeutic for lytic bone diseases.

引用

页数：12