Iron-induced oxidative stress stimulates osteoclast differentiation via NF-κB signaling pathway in mouse model
Abstract
Background Women transitioned to postmenopausal status experience a corresponding gain in iron stores. Recently clinical researches have observed increased serum ferritin level in postmenopausal women, and ferritin level was negatively correlated with bone mineral density.Purpose To explore the mechanism of iron-induced osteopenia in mouse model.Methods Briefly, in this study, we established an iron accumulation mouse model with ovariectomy. Primary osteoclasts and osteoblasts were extracted for this research. Biomarkers of bone metabolism and cell signaling pathways were measured.Results We found that bone mass changed later than ferritin and decreased gradually following overiectomy. We also observed higher levels of bone resorption and oxidative stress when iron was administered. When stimulated with iron, primary osteoclasts derived from bone marrow-derived macrophages (BMMs) underwent differentiation and numerous reactive oxygen species (ROS) were generated. Further, we found that iron activated the JNK, ERK and NF-κB signaling pathways in vivo. In vitro, we found that only NF-κB signaling was stimulated by iron and that suppression of this pathway blocked osteoclast differentiation. To determine whether these effects were related to ROS, osteoclasts were treated with H 2 O 2. We found that ROS stimulated osteoclast activity, and that this effect was reversed upon NF-κB suppression.Conclusions These data suggest that ROS might be a downstream factor of iron and regulated NF-κB signaling in osteoclasts in mouse model.
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Elevated ROS concentrations facilitate osteoclastogenesis by activating NF-κB signaling pathways.
“Elevated ROS concentrations not only directly impair mitochondrial function in BMSCs, thereby inhibiting their osteogenic differentiation potential49, but also facilitate osteoclastogenesis by activating NF-κB signaling pathways50.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [50]
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Iron, Zinc, Copper, Cadmium, Mercury, and Bone Tissue
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“Elevated ROS concentrations not only directly impair mitochondrial function in BMSCs, thereby inhibiting their osteogenic differentiation potential 49 , but also facilitate osteoclastogenesis by activating NF-κ B signaling pathways 50 .”
- Authors
- Wang, X., Chen, B., Sun, J., Jiang, Y., Zhang, H., Zhang, P., Fei, B., & Xu, Y.
- Affiliations
- Second Affiliated Hospital of Soochow University (CN)
- First Affiliated Hospital of Soochow University (CN)
- Soochow University (CN)
- Corresponding author
- Xu, Youjia
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 83
- Pages
- 167-176
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2791780860
- Cited by
- 113
- References
- 32
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 18 · 2023: 15 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 9 · 2018: 5
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81572179)
- Jiangsu Provincial Grant (KYLX16_0159)
- Suzhou Grant (SZZXJ201504, SS201634)
- Hospital preponderant academic subjects group (XKQ2015001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- iron overload, oxidative stress, osteoclastogenesis, NF-κB signaling, reactive oxygen species, postmenopausal osteoporosis, ferritin, bone mineral density, bone resorption, ovariectomy, bone marrow-derived macrophages, hydrogen peroxide
- MeSH terms
- Animals, Bone Resorption, Cell Differentiation, Cells, Cultured, Female, Iron, Mice, Inbred ICR, Osteoclasts, Ovariectomy, Signal Transduction, NF-kappa B, Reactive Oxygen Species, Oxidative Stress, Models, Animal, Mice
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