Open AccessNepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy
Author(s) -
Chu Binxiang,
Chen Shenao,
Zheng Xiaohe,
Ye Jiajing,
Cheng Xu,
Zhang Liwei,
Guo Di,
Wang Peng,
Hong Dun,
Hong Zhenghua
Publication year - 2020
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.16055
Subject(s) - osteolysis , osteoclast , autophagy , rankl , bone resorption , chemistry , mapk/erk pathway , nf κb , microbiology and biotechnology , cancer research , in vivo , signal transduction , in vitro , medicine , apoptosis , biology , activator (genetics) , receptor , biochemistry , dentistry
Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone‐implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti‐inflammatory and anti‐proliferative properties, potently inhibited RANKL‐induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle–induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL‐induced activation of NF‐κB and MAPK signalling pathways and TRAF6‐dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast‐mediated osteolytic diseases.