Aucubin suppresses TLR4/NF-κB signalling to shift macrophages toward M2 phenotype in glucocorticoid-associated osteonecrosis of the femoral head.
J Cell Mol Med
; 28(15): e18583, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39123292
ABSTRACT
In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4/NF-κB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages as well as levels of TLR4/NF-κB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1/M2 ratio, and higher levels of TLR4, MYD88 and NF-κB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose-dependent manner, based on micro-computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF-κB p65. These effects in vivo were confirmed by treating cultures of M1 macrophage-like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4/NF-κB signalling to shift macrophages from a pro- to anti-inflammatory phenotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Receptor 4 Toll-Like
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Fator 88 de Diferenciação Mieloide
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Glucosídeos Iridoides
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Macrófagos
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China