Open AccessAstilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis
Author(s) -
Jin Haiming,
Wang Qingqing,
Chen Kai,
Xu Ke,
Pan Hao,
Chu Feifan,
Ye Zhen,
Wang Ziyi,
Tickner Jennifer,
Qiu Heng,
Wang Chao,
Kenny Jacob,
Xu Huazi,
Wang Te,
Xu Jiake
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14713
Subject(s) - ovariectomized rat , rankl , medicine , chemistry , endocrinology , microbiology and biotechnology , biology , estrogen , activator (genetics) , receptor
Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti‐inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL‐induced formation and function of OCs in a dose‐dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c‐Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption‐related genes and proteins (Acp5/TRAcP, CTSK, V‐ATPase‐d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca 2+ oscillations and the NF‐κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL‐mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.