标题：Mycoepoxydiene suppresses RANKL-induced osteoclast differentiation and reduces ovariectomy-induced bone loss in mice
作者：Zhu, Jingwei; Chen, Qiang; Xia, Xiaochun; Mo, Pingli; Shen, Yuemao; Yu, Chundong
作者机构：[Zhu, Jingwei; Chen, Qiang; Xia, Xiaochun; Mo, Pingli; Yu, Chundong] Xiamen Univ, State Key Lab Cellular Stress Biol, Sch Life Sci, Xiamen, Peoples R 更多
通讯作者地址：[Yu, CD]Xiamen Univ, State Key Lab Cellular Stress Biol, Sch Life Sci, Xiamen, Peoples R China.
来源：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
关键词：Mycoepoxydiene; Osteoclast differentiation; NF-kappa B; ERK1/2; NFATc1
摘要：Mycoepoxydiene (MED) is a compound isolated from the marine fungal Diaporthe sp. HLY-1 associated with mangroves. MED has various biological effects such as anti-microbial, anti-cancer, and anti-inflammatory activities. However, the effect of MED on the differentiation of osteoclasts, the multinucleated bone-resorbing cells which play a crucial role in bone remodeling, is still unknown. In this study, we showed that MED could inhibit receptor activator of NF-kappa B ligand (RANKL)-induced osteoclast differentiation and the expression of three well-known osteoclast markers such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K in bone marrow-derived macrophages. Furthermore, we found that MED inhibited the expression of nuclear factor of activated T cells c1, a key transcriptional factor in osteoclast differentiation, via inhibiting the phosphorylation of TAK1 and then blocking the activation of NF-kappa B and ERK1/2 pathways. Moreover, MED could prevent bone loss in ovariectomized mice. Taken together, we demonstrate for the first time that MED can suppress RANKL-induced osteoclast differentiation in vitro and ovariectomy-induced osteoporosis in vivo, suggesting that MED is a potential lead compound for the development of novel drugs for osteoporosis treatment.