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01-10-2019 | Fracture Healing | Review

Role of Nrf2 in Fracture Healing: Clinical Aspects of Oxidative Stress

Authors: Yusuke Kubo, Christoph Jan Wruck, Athanassios Fragoulis, Wolf Drescher, Hans Christoph Pape, Philipp Lichte, Horst Fischer, Mersedeh Tohidnezhad, Frank Hildebrand, Thomas Pufe, Holger Jahr

Published in: Calcified Tissue International | Issue 4/2019

Abstract

Fracture healing is a natural process that recapitulates embryonic skeletal development. In the early phase after fracture, reactive oxygen species (ROS) are produced under inflammatory and ischemic conditions due to vessel injury and soft tissue damage, leading to cell death. Usually, such damage during the course of fracture healing can be largely prevented by protective mechanisms and functions of antioxidant enzymes. However, intrinsic oxidative stress can cause excessive toxic radicals, resulting in irreversible damage to cells associated with bone repair during the fracture healing process. Clinically, patients with type-2 diabetes mellitus, osteoporosis, habitual drinkers, or heavy smokers are at risk of impaired fracture healing due to elevated oxidative stress. Although increased levels of oxidative stress markers upon fracture and effects of antioxidants on fracture healing have been reported, a detailed understanding of what causes impaired fracture healing under intrinsic conditions of oxidative stress is lacking. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been identified as a key transcriptional regulator of the expression of antioxidants and detoxifying enzymes. It further not only plays a crucial role in preventing degenerative diseases in multiple organs, but also during fracture healing. This narrative review evaluates the influence of intrinsic oxidative stress on fracture healing and sheds new light on the intriguing role of Nrf2 during bone regeneration in pathological fractures.

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Title: Role of Nrf2 in Fracture Healing: Clinical Aspects of Oxidative Stress
Authors: Yusuke Kubo
Christoph Jan Wruck
Athanassios Fragoulis
Wolf Drescher
Hans Christoph Pape
Philipp Lichte
Horst Fischer
Mersedeh Tohidnezhad
Frank Hildebrand
Thomas Pufe
Holger Jahr
Publication date: 01-10-2019
Publisher: Springer US
Keywords: Fracture Healing
Osteoporosis
Osteoporosis
Published in: Calcified Tissue International / Issue 4/2019
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-019-00576-3

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