1. A Nitrobenzoyl Sesquiterpenoid Insulicolide A Prevents Osteoclast Formation via Suppressing c-Fos-NFATc1 Signaling Pathway
- Author
-
Yanhui Tan, Minhong Ke, Zhichao Li, Yan Chen, Jiehuang Zheng, Yiyuan Wang, Xuefeng Zhou, Gang Huang, and Xiaojuan Li
- Subjects
insulicolide A ,osteoclast ,receptor activator of nuclear factor-κB ligand (RANKL) ,LPS ,nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) ,Therapeutics. Pharmacology ,RM1-950 - 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.
- Published
- 2022
- Full Text
- View/download PDF