Hydrogen sulfide protects against IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis in chondrocytes and ameliorates osteoarthritis.
J Cell Physiol
; 236(6): 4369-4386, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33164235
ABSTRACT
The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1ß-induced chondrocytes were identified. Our data revealed decreased H2 S expression in both human degenerative OA cartilage tissue and IL-1ß-induced chondrocytes. Pretreatment with the H2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1ß-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1ß-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1ß-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2 S may antagonize IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Sulfetos
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Apoptose
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Mediadores da Inflamação
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Antirreumáticos
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Condrócitos
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Interleucina-1beta
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Sulfeto de Hidrogênio
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Articulações
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Mitocôndrias
Tipo de estudo:
Observational_studies
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Prognostic_studies
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China