Open AccessMadecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL ‐induced osteoclastogenesis
Author(s) -
Wang Qingqing,
Yao Lingya,
Xu Ke,
Jin Haiming,
Chen Kai,
Wang Ziyi,
Liu Qian,
Cao Zhen,
kenny Jacob,
Liu Yuhao,
Tickner Jennifer,
Xu Huazi,
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.13942
Subject(s) - estrogen , rankl , osteoporosis , endocrinology , medicine , chemistry , pharmacology , cancer research , receptor , activator (genetics)
Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside ( MA ), isolated from Centella asiatica , was reported to have anti‐inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA was found to have an inhibitory effect on the RANKL ‐induced formation and function of OC s in a dose‐dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors ( NFAT c1 and c‐Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption‐related genes and proteins (Acp5/ TRA cP, CTSK , ATP 6V0D2/V‐ ATP ase‐d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses 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, MA might be a potential candidate for treating osteolytic bone diseases.