Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (4): 550-555.doi: 10.12307/2024.215

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Effect of ferroptosis mediated by glutathione peroxidase 4 in the occurrence and progression of synovitis in knee osteoarthritis

Zhang Yaru1, Chen Yanjun2, Zhang Xiaodong2, Chen Shenghua1, Huang Wenhua1, 3    

  1. 1Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, Nanhua University, Hengyang 421001, Hunan Province, China; 2Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China; 
  • Received:2022-12-24 Accepted:2023-02-24 Online:2024-02-08 Published:2023-07-14
  • Contact: Huang Wenhua, Professor, Doctoral supervisor, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, Nanhua University, Hengyang 421001, Hunan Province, China; National Key Disciplines of Human Anatomy, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China Chen Shenghua, MD, Associate professor, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, Nanhua University, Hengyang 421001, Hunan Province, China
  • About author:Zhang Yaru, Master, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, Nanhua University, Hengyang 421001, Hunan Province, China; National Key Disciplines of Human Anatomy, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China
  • Supported by:
    Guangdong Basic and Applied Basic Research Fund, Nos. 2022A1515012545 (CYJ) and 2020B1515120001 (to HWH); Guangdong Provincial Science and Technology Program Project, No. 2017B090912006 (to ZXD)

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Abstract: BACKGROUND: Synovitis plays a leading role in the early progression of knee osteoarthritis and is a potential early therapeutic target. However, the mechanism of synovitis remains unclear. In animal models, increased systemic iron and intracellular iron uptake can induce and exacerbate osteoarthritis, but the association with ferroptosis in synovitis remains unclear. Further studies are needed to investigate the role of ferroptosis in the development and progression of synovitis in osteoarthritis. 
OBJECTIVE: To investigate the role of ferroptosis mediated by glutathione peroxidase 4 (GPX4) in the development of synovitis in knee osteoarthritis. 
METHODS: The synovial tissues of 43 patients with osteoarthritis who underwent arthroscopic or joint replacement surgery and 10 patients undergoing arthroscopic treatment of meniscal injury or ligament tear were collected and divided into three groups according to the Kellgren-Lawrence grading of X-ray images: normal control group (KLG 0, n=10), early knee osteoarthritis group (KLG 1, 2, n=20) and late knee osteoarthritis group (KLG 3, 4, n=23). Hematoxylin-eosin staining was used to observe the severity of synovitis in each group, and iron deposition in the synovium in each group was evaluated by Prussian blue staining. The expressions of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), GPX4, cyclooxygenase 2 and tumor necrosis factor α in the synovium were detected by immunohistochemical staining. Western blot and immunofluorescence were used to detect the expression of ferroptosis-related proteins ACSL4 and GPX4. 
RESULTS AND CONCLUSION: Compared with the normal control group, iron content in synovial tissue was increased in the knee osteoarthritis groups, and iron deposition in the late knee osteoarthritis group was higher than that in the early osteoarthritis group. ACSL4 was highly expressed in the synovial tissue of knee osteoarthritis compared with the normal control group (P < 0.01), and GPX4 was lowly expressed in the synovial tissue of knee osteoarthritis (P < 0.01). The expression level of ACSL4 increased with the progression of osteoarthritis, while the expression level of GPX4 decreased with the progression of osteoarthritis. The expression of cyclooxygenase 2 in the synovium of osteoarthritis was significantly higher than that in the normal synovium, and the expression was the highest in the early stage of osteoarthritis, which was significantly different from that in the advanced stage of osteoarthritis (P < 0.01). The expression of tumor necrosis factor α in the synovium of osteoarthritis was significantly higher than that in the normal synovium, but there was no significant difference between early and late osteoarthritis groups (P > 0.05). To conclude, the deposition of iron exists in the synovial tissue of osteoarthritis and ferroptosis is involved in the occurrence and progression of synovitis in knee osteoarthritis.

Key words: osteoarthritis, synovitis, magnetic resonance image, GPX4, ferroptosis

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