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The detrimental effect of iron on OA chondrocytes: Importance of pro‐inflammatory cytokines induced iron influx and oxidative stress
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Iron overload would promote the expression of chondrocytes catabolic markers, MMP3 and MMP13 expression. In addition, we found that oxidative stress and mitochondrial dysfunction played important roles in iron overload‐induced cartilage degeneration, reducing iron concentration using iron chelator or antioxidant drugs could inhibit iron overload‐induced OA‐related catabolic markers and mitochondrial dysfunction. Our results suggest that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis and promote iron influx, iron overload‐induced oxidative stress and mitochondrial dysfunction play important roles in iron overload‐induced cartilage degeneration.
- Subjects :
- Male
0301 basic medicine
MMP3
Iron Overload
Antioxidant
medicine.medical_treatment
medicine.disease_cause
Proinflammatory cytokine
Mice
03 medical and health sciences
Chondrocytes
0302 clinical medicine
Matrix Metalloproteinase 13
mitochondrial dysfunction
medicine
Animals
Cells, Cultured
Inflammation
Chemistry
Catabolism
Transporter
Original Articles
Cell Biology
In vitro
Cell biology
Mice, Inbred C57BL
Oxidative Stress
osteoarthritis
030104 developmental biology
030220 oncology & carcinogenesis
Cytokines
Molecular Medicine
Matrix Metalloproteinase 3
Original Article
Efflux
Inflammation Mediators
Oxidative stress
pro‐inflammatory cytokines
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....fd6d4487d48ac79d58ed7fe285844658