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. 2024 Sep 30:139:112619.
doi: 10.1016/j.intimp.2024.112619. Epub 2024 Jul 17.

Deferoxamine alleviates chondrocyte senescence and osteoarthritis progression by maintaining iron homeostasis

Zhou Guo  1 , Yang Lin  2 , Haigang Liu  3 , Jiachao Guo  4 , Liangcai Hou  5 , Xiong Zhang  6 , Jingting Xu  7 , Zhaoxuan Ruan  8 , Mi Li  9 , Kai Sun  10 , Fengjing Guo  11
Affiliations

Deferoxamine alleviates chondrocyte senescence and osteoarthritis progression by maintaining iron homeostasis

Zhou Guo et al. Int Immunopharmacol. .

Erratum in

Abstract

Background: Osteoarthritis (OA) is a prevalent age-related disease characterized by the gradual deterioration of cartilage. The involvement of chondrocyte senescence is crucial in the pathogenesis of OA. Desferoxamine (DFO) is an iron chelator with therapeutic potential in various diseases. However, the relationship of chondrocyte senescence and iron homeostasis is largely unknown.

Methods: Chondrocyte senescence was induced using tert-butyl hydroperoxide (TBHP), and the impact of DFO on chondrocyte senescence and iron metabolism was assessed through techniques such as western blotting, qRT-PCR, and β-Galactosidase staining. To assess the impact of DFO on chondrocyte senescence and the progression of osteoarthritis (OA), the surgical destabilization of the medial meniscus model was established.

Results: In chondrocytes, TBHP administration resulted in elevated expression of P16, P21, and P53, as well as alterations in SA-β-gal staining. Nevertheless, DFO effectively mitigated chondrocyte senescence induced by TBHP, and reversed the decrease in collagen II expression and increase in MMP13 expression caused by TBHP. Mechanismly, TBHP induced NCOA4 expression and iron release in chondrocytes. Excessive iron could induce chondrocyte senescence, whereas, DFO could inhibit NCOA4 expression and restore ferritin level, and chelate excessive iron. Importantly, intra-articular injection of DFO enhanced collagen II expression and reduced expression of P16, P21, and MMP13 of cartilage in OA mice, and delayed cartilage degeneration.

Conclusions: Overall, this study provides evidence that DFO has the potential to alleviate chondrocyte senescence induced by TBHP and slow down the progression of osteoarthritis (OA) by effectively chelating excessive iron. These findings suggest that iron chelation could be a promising therapeutic strategy for treating OA.

Keywords: Chondrocyte; Deferoxamine; Iron; Osteoarthritis; Senescence.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Fengjing Guo reports financial support was provided by National Natural Science Foundation of China. Jiachao Guo reports financial support was provided by National Natural Science Foundation of China. Mi Li reports financial support was provided by National Natural Science Foundation of China].

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