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Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-?B and MAPK signalling pathway, and autophagy.

ABSTRACT: 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-?B 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.

SUBMITTER: Chu B 

PROVIDER: S-EPMC7754000 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-κB and MAPK signalling pathway, and autophagy.

Chu Binxiang B   Chen Shenao S   Zheng Xiaohe X   Ye Jiajing J   Cheng Xu X   Zhang Liwei L   Guo Di D   Wang Peng P   Hong Dun D   Hong Zhenghua Z  

Journal of cellular and molecular medicine 20201101 24

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 R  ...[more]

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