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Daphnetin inhibits RANKL‐induced osteoclastogenesis in vitro
Author(s) -
Liu Xifang,
Gao Xiaohang,
Liu Yuanxin,
Liang Dongsheng,
Fu Ting,
Song Yixin,
Zhao Congzhe,
Dong Bo,
Han Weihua
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27555
Subject(s) - rankl , osteoclast , chemistry , cathepsin k , activator (genetics) , nicotinamide adenine dinucleotide phosphate , acid phosphatase , tartrate resistant acid phosphatase , microbiology and biotechnology , in vitro , protein kinase b , signal transduction , reactive oxygen species , receptor , cancer research , biochemistry , biology , oxidase test , enzyme
Osteoporosis is a common orthopedic disease which is associated with hyper‐activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated from Genus Daphne , which possesses antiarthritis effect. However, the role of daphnetin in osteoclastogenesis has not been illustrated. This study aimed to investigate the effects of daphnetin on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis in vitro. Our results showed that the osteoclast formation was significantly suppressed by daphnetin treatment in bone marrow‐derived macrophages (BMMs), which was illustrated by reduced number of tartrate‐resistant acid phosphatase positive multinucleated osteoclasts and decreased expression levels of tumor necrosis factor receptor‐associated factors (TRAF6), c‐Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL caused significant induction effects in reactive oxygen species (ROS) generation and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the induction was dramatically reduced after pretreatment with daphnetin. In addition, daphnetin prevented the RANKL‐induced activation of NF‐κB and Akt/GSK‐3β pathways in BMMs. These findings indicated that daphnetin exhibited an inhibitory effect on RANKL‐induced osteoclastogenesis in vitro. The effect of daphnetin might be mediated by inhibiting ROS signal transduction, as well as preventing the activation of NF‐κB and Akt/GSK‐3β signaling pathways. These findings indicated that daphnetin might be considered as a new therapeutic approach for the osteoporosis treatment.