REVIEW article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1615197
Ferroptosis and Bone Metabolic Diseases: The Dual Regulatory Role of the Nrf2/HO‑1 Signaling Axis
Provisionally accepted
- 1Lanzhou University Second Hospital, Lanzhou, China
- 2Chuxiong People's Hospital, Chuxiong city, China
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Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal mechanism in bone disorders including osteoporosis and osteonecrosis. The nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis plays a paradoxical role—contributing to cytoprotection under oxidative stress, yet potentially promoting ferroptosis through excessive iron accumulation. This review summarizes how the Nrf2/HO-1 pathway modulates ferroptosis across osteoblasts, osteoclasts, and osteocytes, and its impact on bone homeostasis. We explore the pathway's involvement in the shift from physiological bone remodeling to pathological bone loss. Given its dual role, the Nrf2/HO-1 axis represents both a challenge and an opportunity for therapeutic intervention. Understanding its context-specific functions is essential for developing precise, ferroptosis-targeted strategies in bone disease treatment.
Keywords: Nrf2, HO-1, ferroptosis, Bone homeostasis, Oxidative Stress
Received: 20 Apr 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Nan, zhou, zi, shi, dong, song and ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wei Nan, Lanzhou University Second Hospital, Lanzhou, China
yan chao ma, Lanzhou University Second Hospital, Lanzhou, China
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