A Nitrobenzoyl Sesquiterpenoid Insulicolide A Prevents Osteoclast Formation via Suppressing c-Fos-NFATc1 Signaling Pathway

Frontiers in Pharmacology

Pharmacology

Xuefeng Zhou¹  Gang Huang²  Jiehuang Zheng³  Yiyuan Wang³  Minhong Ke³  Xiaojuan Li³  Yan Chen³  Zhichao Li⁴  Yanhui Tan⁵ 

[1] CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China;Integrated Traditional Chinese and Western Medicine Hospital, Southern Medical University, Guangzhou, China;Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China;State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China;State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China;Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China;

关键词: insulicolide A;    osteoclast;    receptor activator of nuclear factor-κB ligand (RANKL);    LPS;    nuclear factor of activated T-cells cytoplasmic 1 (NFATc1);   

DOI  :  10.3389/fphar.2021.753240

 received in 2021-08-04, accepted in 2021-11-19,  发布年份 2022

来源: Frontiers

【 摘 要 】

It is a viable strategy to inhibit osteoclast differentiation for the treatment of osteolytic diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastases. Here we assessed the effects of insulicolide A, a natural nitrobenzoyl sesquiterpenoid derived from marine fungus, on receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and its protective effects on LPS-induced osteolysis mice model in vivo. The results demonstrated that insulicolide A inhibited osteoclastogenesis from 1 μM in vitro. Insulicolide A could prevent c-Fos and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) nuclear translocation and attenuate the expression levels of osteoclast-related genes and DC-STAMP during RANKL-stimulated osteoclastogenesis but have no effects on NF-κB and MAPKs. Insulicolide A can also protect the mice from LPS-induced osteolysis. Our research provides the first evidence that insulicolide A may inhibit osteoclastogenesis both in vitro and in vivo, and indicates that it may have potential for the treatment of osteoclast-related diseases.

【 授权许可】

Unknown   
Copyright © 2022 Tan, Ke, Li, Chen, Zheng, Wang, Zhou, Huang and Li.