Nrf2 Deficiency Impairs Fracture Healing in Mice

作者：Lippross Sebastian^*; Beckmann Rainer; Streubesand Nadine; Ayub Ferda; Tohidnezhad Mersedeh; Campbell Graeme; Kan Yuet Wai; Horst Fischer; Soenmez Tolga Taha; Varoga Deike; Lichte Philipp; Jahr Holger; Pufe Thomas; Wruck Christoph Jan

来源：Calcified Tissue International, 2014, 95(4): 349-361.

DOI：10.1007/s00223-014-9900-5

• Nrf2
• Fracture healing
• Bone
• Knock out mouse

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, A mu CT 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.

• 出版日期2014-10