Characteristics and time points to inhibit ferroptosis in human osteoarthritis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
received:
07
08
2023
accepted:
04
12
2023
medline:
8
12
2023
pubmed:
8
12
2023
entrez:
7
12
2023
Statut:
epublish
Résumé
Ferroptosis is a form of cell death that is triggered by iron-dependent lipid peroxidation and is closely associated with osteoarthritis. The primary interventions for inhibiting ferroptosis in osteoarthritis are anti-lipid peroxidation and iron chelation. The objective of our study is to investigate the characteristics of ferroptosis in osteoarthritis and identify the optimal time points for inhibiting ferroptosis to alleviate disease progression. Ferroptosis-related alterations and markers of OA were analyzed in paired intact and damaged cartilages from OA patients by immunofluorescence, qRT-PCR, mitochondrial membrane potential and immunohistochemistry. We also compared Ferroptosis-related alterations in cartilage of mild, moderate, and severe OA (according to the modified Mankin score). In addition, we compared the effect of Fer-1 on ferroptosis and the protection of chondrocytes by detecting markers of both ferroptosis and OA by immunofluorescence, CCK8 and qRT-PCR. Ferroptosis-related alterations (GPX4 downregulation, ACSL4 upregulation, MDA, LPO accumulation, Mitochondrial membrane potential decreased) in the damaged area cartilage were more severe than those in the intact area and increased with the progression of OA. Compared with mild OA group, the activity of chondrocytes treated with Fer-1 (a ferroptosis inhibitor) was increased, mitochondrial function was improved, and ferroptosis was reduced (GPX4 upregulation, SLC7A11 upregulation, ACSL4 downregulation,), and promoted the expression of COL2A1 and inhibited the expression of MMP13. However, these changes were not observed in moderate and severe OA chondrocytes. Ferroptosis occurs in a region-specific manner and is exacerbated with the progression of human OA cartilage degeneration. Inhibition of ferroptosis might had a therapeutic effect on chondrocytes with mild OA but had no significant therapeutic effect on chondrocytes with moderate to severe OA.
Identifiants
pubmed: 38062071
doi: 10.1038/s41598-023-49089-y
pii: 10.1038/s41598-023-49089-y
pmc: PMC10703773
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21592Informations de copyright
© 2023. The Author(s).
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