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Ferroptosis: a new target for iron overload-induced hemophilic arthropathy synovitis

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Abstract

Iron deposition is closely related to developing haemophilic arthropathy (HA). Studying the relationship between ferroptosis signal expression and iron overload in HA synovium facilitates understanding the pathogenesis of joint synovial hyperplasia in bloodborne arthritis and the development of new protective methods. The knee synovium was collected from HA and osteoarthritis (OA) patients, and pathological changes were analysed by HE and Prussian blue staining. Ferroptosis phenotypes were examined by immunohistochemistry and western blotting. Moreover, ferric ammonium citrate (FAC)-induced was used to construct an in vitro iron overload model to investigate the relationship between iron overload and ferroptosis in synovial fibroblasts (FLS). Furthermore, the factors influencing ferroptosis in FLS were explored. Iron deposition, cell proliferation, and vascular proliferation in the synovium of HA were more obvious. Ferroptosis in HA synovium appears to inhibit. FLS ferroptosis increased with iron accumulation, malondialdehyde (MDA) in cells, and glutathione (GSH) depletion. TNF-α plays a protective role in this process. Blocking the action of TNF-α and inducing ferroptosis significantly reduced synovial proliferation. TNF-α inhibitors combined with a ferroptosis inducer may be a new therapeutic method for HA synovitis.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Author notes

  1. Zhiwei Han, Liujie Zheng, and Dasheng Luo contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, Anhui, China

    Zhiwei Han, Dasheng Luo, Nanyu Pang & Yunfeng Yao

  2. Department of Orthopaedic Surgery, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.473 Hanzheng Street, Wuhan, HuBei, China

    Liujie Zheng

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Contributions

Han and Yao designed the research study and wrote the paper. Han, Zheng, and Luo conducted the experiments and revised the paper. Pang analysed the data. All the authors critically reviewed successive drafts of the manuscript and have approved the final version.

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Correspondence to Yunfeng Yao.

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The Ethics Review Committee of the Second Affiliated Hospital of Anhui Medical University approved this study.

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Han, Z., Zheng, L., Luo, D. et al. Ferroptosis: a new target for iron overload-induced hemophilic arthropathy synovitis. Ann Hematol 102, 1229–1237 (2023). https://doi.org/10.1007/s00277-023-05190-w

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  • DOI: https://doi.org/10.1007/s00277-023-05190-w

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