FoxO1 Transcription Factor in Chondrocyte Regulation: A Review on Its Molecular Mechanisms, Pathological Roles, and Therapeutic Potential

Authors

  • Ting Chen, Mei hua Tan, Kai Bin Liew

Abstract

FoxO1 as a transcription factor integrates multiple signals for maintaining cartilage homeostasis, and it is the most essential regulator of chondrocyte activities. Activity of chondrocytes involving proliferation, differentiation, stress resistance, and autophagy modulation is controlled by FoxO1 via perturbations in phosphorylation and acetylation, alongside its conserved forkhead DNA-binding domain. Notable FoxO1 actions include: cooperation with Sox9 for ECM synthesis, inhibition of hypertrophic differentiation via β-catenin sequestration, increase of stress tolerance, and elevation of antioxidant and autophagy-related gene activity. Decline of apoptotic signaling and enhanced cytosolic cleansing mechanisms related to aging and chronic inflammation under dysregulated FoxO1 drives osteoarthritis development due to disruption to the uncontrollably worsening autophagic flux, increased ECM breakdown, apoptosis and cellular senescence. FoxO1’s sensitivity to growth factors, oxidative stress, and metabolic signals is tuned via PI3K/Akt, AMPK/Sirt1, Wnt/β-catenin pathways crosstalk. Therapeutic approaches aiming to restore the favorable actions of FoxO1 include: gene therapies using viral vectors, CRISPR-based methods, and pharmacological targeting of upstream regulators like Sirt1 and AMPK. This review in total positions FoxO1 as a chondrocyte master regulator while pinpointing rounded therapeutic intersections.

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2025-05-14

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Ting Chen, Mei hua Tan, Kai Bin Liew. FoxO1 Transcription Factor in Chondrocyte Regulation: A Review on Its Molecular Mechanisms, Pathological Roles, and Therapeutic Potential. J Neonatal Surg [Internet]. 2025May14 [cited 2025Sep.28];14(18S):1242-54. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/6281

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Vol. 14 No. 18S (2025): Journal of Neonatal Surgery

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