International Journal of General Medicine (May 2024)

IGF2BP1 Bolsters the Chondrocytes Ferroptosis of Osteoarthritis by Targeting m6A/MMP3 Axis

  • Zhao Z,
  • Dong S,
  • Yang Y,
  • Yin H,
  • Xiong G,
  • Ma J

Journal volume & issue
Vol. Volume 17
pp. 2433 – 2443

Abstract

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Ziqin Zhao,1 Shuhui Dong,1 Yong Yang,1 Haibo Yin,1 Guangyi Xiong,1 Jianxiong Ma2 1Department of Pathology, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 2Institute of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Jianxiong Ma, Institute of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China, Email [email protected]: Chondrocyte degeneration and senescence are characteristics of osteoarthritis (OA) and other joint degenerative diseases, and ferroptosis has been observed to regulate the development of OA. However, the role of the N6-methyladenosine (m6A) modification in OA ferroptosis remains unclear.Methods: This study performed series of assays to investigate the function of the m6A reader IGF2BP1 in OA ferroptosis, including m6A quantitative analysis, Iron (Fe2+) release analysis, Malondialdehyde (MDA) measurement, lipid peroxidation (ROS) detection and Glutathione (GSH) measurement. The molecular interaction and mechanism analysis was performed by Luciferase reporter assay, mRNA stability analysis and RNA immunoprecipitation (RIP) assay.Results: These results indicate that IGF2BP1 is upregulated in IL-1β-induced chondrocytes. Functionally, IGF2BP1 silencing represses ferroptosis, including iron (Fe2+) accumulation, malondialdehyde, and reactive oxygen species (ROS). Mechanistically, among the potential downstream targets, matrix metalloproteinase-3 (MMP3) was observed to harbor a significant m6A modified site in the 3’-UTR. IGF2BP1 combines with MMP3 through the binding of m6A sites, thereby enhancing MMP3 mRNA stability.Discussion: In conclusion, our findings revealed the functions and mechanisms of m6A regulator IGF2BP1 in OA chondrocyte’s ferroptosis, providing a novel target for OA treatment.Keywords: osteoarthritic cartilage, IGF2BP1, ferroptosis, MMP3

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