Inhibition of JNK and activation of the AMPK-Nrf2 axis by corosolic acid suppress osteolysis and oxidative stress.
Nitric Oxide
; 82: 12-24, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30453049
ABSTRACT
The intracellular reactive oxygen species contribute to RANKL-induced osteoclastogenesis and osteolysis. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a redox-sensitive transcription factor, is critical in the cellular defense against oxidative stress by induction of antioxidants and cytoprotective enzymes. In the current study, it was first demonstrated that RANKL-induced osteoclastogenesis and hydroxylapatite resorption were suppressed by Corosolic acid (CA) via inhibiting p-JNK and activating p-AMPK. Meanwhile, p-65, p-38, Akt, and GSK-3ß were partly inhibited during the treatment of CA. Osteoclastogenesis related genes, including NFATc1, c-fos, cathepsin K, and CTR were down-regulated by CA as well. Furthermore, the intracellular oxidative stress of CA-treated osteoclasts was dramatically decreased and Nrf2 was translocated into the nucleus to activate antioxidants including HO-1, NQO-1, and GCLC by CA. The LPS-induced mice calvarial osteolysis model was established for the in vivo investigation. Micro-CT morphometric analysis revealed that the treatment of CA restored LPS-induced bone loss and formation of osteoclasts. Besides, p-p65 and p-JNK were activated in the LPS group but inhibited by CA in vivo. The treatment of CA also activated p-AMPK during its attenuating LPS-induced osteolysis. Conclusively, CA effectively protects against LPS-induced osteolysis by suppressing osteoclastogenesis and oxidative stress through the inhibition of the JNK and activation of the AMPK-Nrf2 axis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteólise
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Triterpenos
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Proteínas Quinases JNK Ativadas por Mitógeno
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Fator 2 Relacionado a NF-E2
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Proteínas Quinases Ativadas por AMP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article