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Updated: Apr 26, 2026
The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing
Published on: August 16, 2018
Nrf2 deficiency impairs fracture healing in mice
Sebastian Lippross1, Rainer Beckmann, Nadine Streubesand
1Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Kiel, Germany, Sebastian.lippross@uksh-kiel.de.
Abstract:
Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.
Insights
Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial for bone healing. Nrf2 deficiency in mice impaired fracture healing, showing reduced callus formation and strength, highlighting Nrf2
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Skeletal Biology
Background:
- Oxidative stress impacts wound healing, but its role in fracture healing is less understood.
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant defenses.
- Nrf2's specific role in bone regeneration requires further investigation.
Purpose of the Study:
- To investigate the role of Nrf2 in bone fracture healing.
- To compare fracture healing in wild-type (WT) and Nrf2-knockout (Nrf2-KO) mice.
- To assess the impact of Nrf2 deficiency on bone healing processes and outcomes.
Main Methods:
- Utilized a standard closed femoral shaft fracture model in WT and Nrf2-KO mice.
- Evaluated fracture healing through histological analysis, real-time RT-PCR, micro-computed tomography (µCT), and biomechanical testing.
- Measured gene expression of key healing markers like VEGF and osteocalcin.
Main Results:
- Nrf2 expression was activated during the fracture healing process.
- Nrf2-KO mice exhibited retarded bone healing and remodeling compared to WT mice.
- Nrf2-KO mice showed significantly reduced callus formation, lower biomechanical strength, and decreased VEGF and osteocalcin expression.
Conclusions:
- Nrf2 plays an essential role in bone regeneration and fracture healing.
- Nrf2 deficiency leads to impaired fracture healing outcomes in mice.
- Targeting Nrf2 pharmacologically presents a potential therapeutic strategy for enhancing fracture repair.
