AUTHOR=Tan Yanhui , Ke Minhong , Li Zhichao , Chen Yan , Zheng Jiehuang , Wang Yiyuan , Zhou Xuefeng , Huang Gang , Li Xiaojuan TITLE=A Nitrobenzoyl Sesquiterpenoid Insulicolide A Prevents Osteoclast Formation via Suppressing c-Fos-NFATc1 Signaling Pathway JOURNAL=Frontiers in Pharmacology VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.753240 DOI=10.3389/fphar.2021.753240 ISSN=1663-9812 ABSTRACT=It is a viable strategy to inhibit osteoclast differetiation 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 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 NFATc1 nuclear translocation and attenuate the expression levels of osteoclast-relatived 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.