GPX4-Mediated Inhibition of Ferroptosis by Sodium Selenite Ameliorates Bone Metabolic Disorders in Ovariectomized Mice.
4 affiliations
- 1The Department of Orthopedic Surgery, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China.
- 2The Department of Orthopedic Surgery, Taizhou Fourth People's Hospital, Taizhou, Jiangsu, China.
- 3The Department of Orthopaedic Surgery, Orthopaedic Institute, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
- 4College of Chemistry, Chemical Engineering and Materials Science Soochow University, Suzhou, People's Republic of China.
Abstract
Postmenopausal osteoporosis (PMOP) and its associated fracture complications have emerged as pressing public health challenges due to rapidly accelerating global population ageing. The functional decline of bone marrow mesenchymal stem cells (BMSCs) under elevated oxidative stress is a recognised pathogenic cornerstone of PMOP, positioning redox imbalance as a critical therapeutic node. Here, we establish that sodium selenite (Na₂SeO₃) robustly counters oxidative insults in BMSCs, thereby restoring and enhancing their osteogenic lineage commitment. Furthermore, RNA sequencing analysis indicated that ferroptosis may be mechanistically associated with the underlying cellular responses. Ferroptosis is critically mediated by glutathione peroxidase 4 (GPX4), a selenoenzyme that functions as its principal enzymatic suppressor. Silencing GPX4 in BMSCs markedly reduced their osteogenic capacity and simultaneously upregulated ferroptotic protein expression. Notably, this impairment was not reversed by Na₂SeO₃ administration under conditions of GPX4 suppression. These findings suggest that Na₂SeO₃ enhances osteogenic differentiation primarily by upregulating GPX4 expression, thereby inhibiting ferroptosis. Thus, we have established Na₂SeO₃ as a potential therapeutic strategy for PMOP by identifying a previously unrecognised molecular axis through which selenium regulates bone metabolic homeostasis.
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BibTeX
@article{luo2026gpx4mediated,
title = {{GPX4-Mediated Inhibition of Ferroptosis by Sodium Selenite Ameliorates Bone Metabolic Disorders in Ovariectomized Mice.}},
author = {Wei Luo and Haibo Xu and Xin Liu and Yongsheng Zhang and Hao Zhou and Xiangqiang Pan and Dechun Geng and Hanliang He},
journal = {Journal of cellular and molecular medicine},
year = {2026},
month = oct,
doi = {10.1111/jcmm.71414},
url = {https://europepmc.org/article/MED/42895130},
note = {CC BY},
}
RIS
TY - JOUR
TI - GPX4-Mediated Inhibition of Ferroptosis by Sodium Selenite Ameliorates Bone Metabolic Disorders in Ovariectomized Mice.
AU - Wei Luo
AU - Haibo Xu
AU - Xin Liu
AU - Yongsheng Zhang
AU - Hao Zhou
AU - Xiangqiang Pan
AU - Dechun Geng
AU - Hanliang He
PY - 2026
DA - 2026/10/01
JO - Journal of cellular and molecular medicine
DO - 10.1111/jcmm.71414
UR - https://europepmc.org/article/MED/42895130
AB - Postmenopausal osteoporosis (PMOP) and its associated fracture complications have emerged as pressing public health challenges due to rapidly accelerating global population ageing. The functional decline of bone marrow mesenchymal stem cells (BMSCs) under elevated oxidative stress is a recognised pathogenic cornerstone of PMOP, positioning redox imbalance as a critical therapeutic node. Here, we establish that sodium selenite (Na₂SeO₃) robustly counters oxidative insults in BMSCs, thereby restoring and enhancing their osteogenic lineage commitment. Furthermore, RNA sequencing analysis indicated that ferroptosis may be mechanistically associated with the underlying cellular responses. Ferroptosis is critically mediated by glutathione peroxidase 4 (GPX4), a selenoenzyme that functions as its principal enzymatic suppressor. Silencing GPX4 in BMSCs markedly reduced their osteogenic capacity and simultaneously upregulated ferroptotic protein expression. Notably, this impairment was not reversed by Na₂SeO₃ administration under conditions of GPX4 suppression. These findings suggest that Na₂SeO₃ enhances osteogenic differentiation primarily by upregulating GPX4 expression, thereby inhibiting ferroptosis. Thus, we have established Na₂SeO₃ as a potential therapeutic strategy for PMOP by identifying a previously unrecognised molecular axis through which selenium regulates bone metabolic homeostasis.
SN - 1582-1838
SN - 1582-4934
ER -