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Glutathione peroxidase 4 as an emerging therapeutic target in osteoarthritis: focus on ferroptosis

Lin Zhang1, Jinglin Li1, Xuxu Yang1

  • 1Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Frontiers in Cell and Developmental Biology
|January 28, 2026
PubMed

Insights

Glutathione peroxidase 4 (GPX4) plays a key role in osteoarthritis by regulating ferroptosis, a cell death process. Targeting GPX4 offers promising new therapeutic strategies for treating osteoarthritis.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Pathology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with limited treatment options.
  • Ferroptosis, an iron-dependent cell death, is increasingly recognized in OA pathogenesis.
  • Glutathione peroxidase 4 (GPX4) is a critical inhibitor of ferroptosis, with altered expression in OA.

Purpose of the Study:

  • To review the role of GPX4 in osteoarthritis pathogenesis.
  • To explore therapeutic strategies targeting GPX4 for OA treatment.
  • To discuss challenges and future directions for clinical translation.

Main Methods:

  • Literature review of experimental evidence linking GPX4 and ferroptosis in OA.
  • Analysis of molecular mechanisms regulating GPX4.
  • Summary of current and potential therapeutic interventions.

Main Results:

  • GPX4's expression and activity are altered in OA cartilage.
  • GPX4 inhibition promotes ferroptosis, contributing to OA.
  • Targeting GPX4 presents potential therapeutic avenues for OA.

Conclusions:

  • GPX4 is a crucial mediator in OA pathogenesis via ferroptosis.
  • Therapeutic strategies targeting GPX4 show promise for OA treatment.
  • Further research is needed to translate GPX4-based therapies into clinical practice.
Keywords:
GPX4chondrocyteextracellular matrixferroptosisosteoarthritis

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