The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.

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.

• Authors: Xingzhi Jing, Ting Du, Tao Li, Xiaoxia Yang, Guodong Wang, Xiaoyang Liu, Zhensong Jiang, Xingang Cui
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 12 Pg. 5671-5680 (06 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33942503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Cytokines
• Inflammation Mediators
• MMP13 protein, human
• Matrix Metalloproteinase 13
• MMP3 protein, human
• Matrix Metalloproteinase 3

Topics

• Animals
• Cells, Cultured
• Chondrocytes (metabolism, pathology)
• Cytokines (toxicity)
• Inflammation (complications)
• Inflammation Mediators (toxicity)
• Iron Overload (complications)
• Male
• Matrix Metalloproteinase 13 (genetics, metabolism)
• Matrix Metalloproteinase 3 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Osteoarthritis (etiology, metabolism, pathology)
• Oxidative Stress