Mycoepoxydiene suppresses RANKL-induced osteoclast differentiation and reduces ovariectomy-induced bone loss in mice.
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-κB 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-κB 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.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Jingwei
J
Zhu
Qiang
Q
Chen
Xiaochun
X
Xia
Pingli
P
Mo
Yuemao
Y
Shen
Chundong
C
Yu
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010052:Ovariectomy; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use*; D053245:RANK Ligand / Q000494:pharmacology*
D001952:Bridged-Ring Compounds; D011753:Pyrones; D053245:RANK Ligand; C476085:mycoepoxydiene