GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL1ß, via a mechanism mediated by ferroptosis.
Mol Med Rep
; 30(1)2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38757339
ABSTRACT
During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokineinduced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)1ß, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL1ß treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL1ßinduced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OArelated research and may enable the development of translational strategies for the treatment of OA.
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Base de dados:
MEDLINE
Assunto principal:
Condrócitos
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Matriz Extracelular
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Interleucina-1beta
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Ferroptose
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Glutationa Peroxidase
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Inflamação
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article