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

Yanhui Tan; Minhong Ke; Zhichao Li; Yan Chen; Jiehuang Zheng; Yiyuan Wang; Xuefeng Zhou; Gang Huang; Xiaojuan Li

doi:10.3389/fphar.2021.753240

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

Front Pharmacol. 2022 Jan 17:12:753240. doi: 10.3389/fphar.2021.753240. eCollection 2021.

Authors

Yanhui Tan^{1

2}, Minhong Ke², Zhichao Li¹, Yan Chen², Jiehuang Zheng², Yiyuan Wang², Xuefeng Zhou³, Gang Huang⁴, Xiaojuan Li²

Affiliations

¹ 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.
² Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
³ 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.
⁴ Integrated Traditional Chinese and Western Medicine Hospital, Southern Medical University, Guangzhou, China.

Abstract

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.

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