Experimental study on the effect of the local iron ionic microenvironment on bone healing in bone defects
- 1Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Oral and Maxillofacial Surgery, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai 200072, China
Abstract
[Objective:] To investigate the changes in local iron ion levels following mandibular bone defects and evaluate the effect of desferrioxamine (DFO) on bone defect repair, as well as to preliminarily explore the underlying mechanism by which DFO promotes osteogenic differentiation. [Methods:] A mouse mandibular bone defect model was established. Local iron deposition was evaluated by Prussian blue staining and tissue iron content assay. DFO was locally administered, and bone defect repair was assessed using Micro-CT. An iron overload microenvironment was established in vitro using ferric ammonium citrate (FAC). Cell viability was assessed by CCK-8 assay. Osteogenic differentiation was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, alkaline phosphatase (ALP) staining, and alizarin red S staining. The expression of hypoxia-inducible factor-1α (HIF-1α) and mitophagy-related molecules was detected by immunofluorescence staining, RT-qPCR, and Western blotting. Small interfering RNA (siRNA)-mediated HIF-1α knockdown and the mitophagy inhibitor 3-methyladenine (3-MA) were used to further investigate the underlying mechanism. [Results:] Increased local iron deposition and significantly elevated tissue iron content were observed following mandibular bone defects in mice. Local administration of DFO promoted new bone formation and improved bone microarchitectural parameters in the defect area. In vitro, the iron overload microenvironment suppressed the expression of osteogenesis-related genes and proteins, reduced ALP activity, and inhibited mineralized nodule formation, whereas DFO partially reversed these effects. Furthermore, DFO upregulated the expression of HIF-1α and mitophagy-related molecules. The promotive effect of DFO on osteogenic differentiation was markedly attenuated after HIF-1α knockdown or treatment with 3-MA. [Conclusion:] Iron ion levels are elevated in the bone defect area. Iron overload impairs osteogenic differentiation, while DFO counteracts this inhibition via mitophagy-mediated enhancement of osteogenesis.
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BibTeX
@article{rui2026experimental,
title = {{Experimental study on the effect of the local iron ionic microenvironment on bone healing in bone defects}},
author = {HUANG Rui and CHENG Chunan and KANG Feiwu},
journal = {Kouqiang hemian waike zazhi},
year = {2026},
month = oct,
doi = {10.12439/kqhm.1005-4979.2026.05.003},
url = {https://doi.org/10.12439/kqhm.1005-4979.2026.05.003},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Experimental study on the effect of the local iron ionic microenvironment on bone healing in bone defects
AU - HUANG Rui
AU - CHENG Chunan
AU - KANG Feiwu
PY - 2026
DA - 2026/10/30
JO - Kouqiang hemian waike zazhi
DO - 10.12439/kqhm.1005-4979.2026.05.003
UR - https://doi.org/10.12439/kqhm.1005-4979.2026.05.003
AB - [Objective:] To investigate the changes in local iron ion levels following mandibular bone defects and evaluate the effect of desferrioxamine (DFO) on bone defect repair, as well as to preliminarily explore the underlying mechanism by which DFO promotes osteogenic differentiation. [Methods:] A mouse mandibular bone defect model was established. Local iron deposition was evaluated by Prussian blue staining and tissue iron content assay. DFO was locally administered, and bone defect repair was assessed using Micro-CT. An iron overload microenvironment was established in vitro using ferric ammonium citrate (FAC). Cell viability was assessed by CCK-8 assay. Osteogenic differentiation was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, alkaline phosphatase (ALP) staining, and alizarin red S staining. The expression of hypoxia-inducible factor-1α (HIF-1α) and mitophagy-related molecules was detected by immunofluorescence staining, RT-qPCR, and Western blotting. Small interfering RNA (siRNA)-mediated HIF-1α knockdown and the mitophagy inhibitor 3-methyladenine (3-MA) were used to further investigate the underlying mechanism. [Results:] Increased local iron deposition and significantly elevated tissue iron content were observed following mandibular bone defects in mice. Local administration of DFO promoted new bone formation and improved bone microarchitectural parameters in the defect area. In vitro, the iron overload microenvironment suppressed the expression of osteogenesis-related genes and proteins, reduced ALP activity, and inhibited mineralized nodule formation, whereas DFO partially reversed these effects. Furthermore, DFO upregulated the expression of HIF-1α and mitophagy-related molecules. The promotive effect of DFO on osteogenic differentiation was markedly attenuated after HIF-1α knockdown or treatment with 3-MA. [Conclusion:] Iron ion levels are elevated in the bone defect area. Iron overload impairs osteogenic differentiation, while DFO counteracts this inhibition via mitophagy-mediated enhancement of osteogenesis.
SN - 1005-4979
ER -