Cycloastragenol Attenuates Osteoclastogenesis and Bone Loss by Targeting RANKL-Induced Nrf2/Keap1/ARE, NF-κB, Calcium, and NFATc1 Pathways

被引：35

作者：

Wang, Gang ^{[1
,2
,3
]}

Ma, Chao ^{[3
]}

Chen, Kai ^{[2
]}

Wang, Ziyi ^{[2
]}

Qiu, Heng ^{[2
]}

Chen, Delong ^{[2
,3
]}

He, Jianbo ^{[2
,3
]}

Zhang, Cheng ^{[3
]}

Guo, Ding ^{[3
]}

Lai, Boyong ^{[3
]}

Zhang, Shuangxiao ^{[3
]}

Huang, Linfeng ^{[3
]}

Yang, Fan ^{[3
]}

Yuan, Jinbo ^{[2
]}

Chen, Leilei ^{[3
,4
]}

He, Wei ^{[3
,4
]}

Xu, Jiake ^{[2
]}

机构：

[1] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China

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

[3] Guangzhou Univ Chinese Med, Guangzhou, Guangdong, Peoples R China

[4] Guangzhou Univ Chinese Med, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 12卷

基金：

英国医学研究理事会; 中国国家自然科学基金;

关键词：

cycloastragenol; osteoclast; RANKL; Nfatc1; ROS; RECEPTOR ACTIVATOR; DIFFERENTIATION; EXPRESSION; INHIBITION; INDUCTION; FRACTURE; CLONING; LIGAND; WOMEN; RISK;

D O I：

10.3389/fphar.2021.810322

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Osteoporosis, which typically affects postmenopausal women, is an osteolytic disease due to over-activation of osteoclasts. However, current drugs targeting osteoclast inhibition face various side effects, making natural compounds with great interest as alternative treatment options. Cycloastragenol (CAG) is a triterpenoid with multiple biological activities. Previously, CAG's activity against aging-related osteoporosis was reported, but the mechanisms of actions for the activities were not understood. This study demonstrated that CAG dose-dependently inhibited osteoclast formation in receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated bone marrow macrophage (BMMs). Mechanism studies showed that CAG inhibited NF-kappa B, calcium, and nuclear factor of activated T cells 1 (NFATc1) pathways. Additionally, CAG also promoted the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/anti-oxidative response element (ARE) pathway that scavenges reactive oxygen species (ROS). Furthermore, CAG was also found to prevent bone loss of postmenopausal osteoporosis (PMO) in a preclinical model of ovariectomized (OVX) mice. Collectively, our research confirms that CAG inhibits the formation and function of osteoclasts by regulating RANKL-induced intracellular signaling pathways, which may represent a promising alternative for the therapy of osteoclast-related disease.

引用

页数：13

共 43 条

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