Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-κB and MAPK signalling pathway, and autophagy.
J Cell Mol Med
; 24(24): 14366-14380, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33135301
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-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Autofagia
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Transdução de Sinais
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NF-kappa B
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Proteínas Quinases Ativadas por Mitógeno
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Flavonas
Limite:
Animals
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China