Open AccessEvodiamine inhibits RANKL ‐induced osteoclastogenesis and prevents ovariectomy‐induced bone loss in mice
Author(s) -
Jin Haiming,
Yao Lingya,
Chen Kai,
Liu Yuhao,
Wang Qingqing,
Wang Ziyi,
Liu Qian,
Cao Zhen,
Kenny Jacob,
Tickner Jennifer,
Wang Xiangyang,
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.13955
Subject(s) - rankl , osteoclast , ovariectomized rat , bone resorption , in vivo , chemistry , osteolysis , endocrinology , medicine , activator (genetics) , receptor , osteoporosis , microbiology and biotechnology , biology , estrogen , surgery
Postmenopausal osteoporosis ( PMO ) is a progressive bone disease characterized by the over‐production and activation of osteoclasts in elderly women. In our study, we investigated the anti‐osteoclastogenic effect of evodiamine ( EVO ) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage ( BMM )‐derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF ‐κB ligand ( RANKL )‐induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL ‐induced transcriptional activity of IκBα. RANKL ‐induced Ca 2+ oscillations were also abrogated by EVO . In vivo, an ovariectomized ( OVX ) mouse model was established to mimic PMO , and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL ‐induced osteoclastogenesis through NF ‐κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO .