Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation

被引：41

作者：

Chen, Delong ^{[1
,2
]}

Ye, Zhen ^{[3
]}

Wang, Chao ^{[2
]}

Wang, Qingqing ^{[2
,4
]}

Wang, Haibin ^{[5
]}

Kuek, Vincent ^{[2
]}

Wang, Ziyi ^{[2
]}

Qiu, Heng ^{[2
]}

Yuan, Jinbo ^{[2
]}

Kenny, Jacob ^{[2
]}

Yang, Fan ^{[6
,7
]}

He, Jianbo ^{[2
,8
]}

Liu, Yun ^{[2
,9
]}

Wang, Gang ^{[2
,8
]}

Zhang, Meng ^{[8
]}

Zhang, Gangyu ^{[8
]}

Wang, Junjian ^{[10
]}

Chen, Peng ^{[5
]}

Xu, Jiake ^{[2
]}

机构：

[1] Jinan Univ, Clifford Hosp, Dept Orthopaed Surg, Guangzhou 510006, Peoples R China

[2] Univ Western Australia, Sch Biomed Sci, Perth, WA 6009, Australia

[3] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325000, Peoples R China

[4] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Orthopaed Surg, Sch Med, Hangzhou 310000, Peoples R China

[5] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Orthopaed Surg, Guangzhou 510405, Peoples R China

[6] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai 201203, Peoples R China

[7] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, SHTCM Key Lab New Resources & Qual Evaluat Chines, Shanghai 201203, Peoples R China

[8] Guangzhou Univ Chinese Med, Guangzhou 510405, Peoples R China

[9] Guangxi Med Univ, Affiliated Hosp 1, Dept Spine Osteopathy Surg, Nanning 530021, Peoples R China

[10] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China

来源：

PHARMACOLOGICAL RESEARCH | 2020年 / 159卷

基金：

中国国家自然科学基金; 英国医学研究理事会; 中国博士后科学基金;

关键词：

Arctiin; Osteoclast; Bone resorption; RANKL-induced NFATc1 activation; ROS; INHIBITS OSTEOCLASTOGENESIS; RECEPTOR ACTIVATOR; NATURAL-PRODUCTS; NUCLEAR-FACTOR; OSTEOPOROSIS; DIFFERENTIATION; MECHANISMS; EXPRESSION; PATHOGENESIS; CLONING;

D O I：

10.1016/j.phrs.2020.104944

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-kappa B ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby(2) preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis.

引用

页数：13

共 54 条

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