Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
Department of Orthopaedics, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Calcif Tissue Int. 2019 Oct;105(4):341-352. doi: 10.1007/s00223-019-00576-3. Epub 2019 Jun 24.
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.
骨折愈合是一个自然的过程，它重现了胚胎骨骼的发育。在骨折后的早期阶段，由于血管损伤和软组织损伤，反应性氧物种（ROS）在炎症和缺血条件下产生，导致细胞死亡。通常，在骨折愈合过程中，这种损伤可以通过抗氧化酶的保护机制和功能来很大程度上预防。然而，内在的氧化应激会导致过多的有毒自由基，从而导致与骨折愈合过程中骨修复相关的细胞不可逆转的损伤。临床上，患有 2 型糖尿病、骨质疏松症、习惯性饮酒者或重度吸烟者，由于氧化应激升高，存在骨折愈合受损的风险。尽管已经报道了骨折时氧化应激标志物水平升高以及抗氧化剂对骨折愈合的影响，但对于内在氧化应激条件下导致骨折愈合受损的原因仍缺乏详细的了解。核因子红细胞 2 相关因子 2（Nrf2）已被确定为抗氧化剂和解毒酶表达的关键转录调节因子。它不仅在预防多个器官的退行性疾病方面发挥着至关重要的作用，而且在骨折愈合过程中也发挥着重要作用。本综述评估了内在氧化应激对骨折愈合的影响，并揭示了 Nrf2 在病理性骨折骨再生过程中的作用。
