【摘要】 骨质疏松症（Osteoporosis, OP）是一种以骨密度和骨强度降低、骨骼脆性和骨折风险增加为特征的骨骼疾病。随着老年化社会的到来，OP及其所引起的骨折已成为严重危害人类健康的世界性公共卫生问题，但目前关于调节骨质疏松的病理机制仍不明确。转录激活因子4(Activating transcription factor 4,ATF4)是调节线粒体及内质网应激的重要转录因子，而核转录因子红系2相关因子2(Nuclear factor-erythroid 2-related factor 2,Nrf2)是细胞防御化学/氧化应激的重要调节因子，它们在骨质疏松病理过程中发挥着重要作用，成为新的研究热点。本综述概述了ATF4/Nrf2在OP发生发展中的作用。ATF4不仅可作为Wnt/β-catenin信号通路调节成骨细胞形成、分化的关键因子，促进骨髓间充质干细胞向成骨细胞分化，还可以通过内质网应激上调PERK/eIF2α/CHOP信号通路，促进成骨细胞凋亡。Nrf2主要通过调控ROS，减轻成骨细胞氧化损伤，同时，Nrf2可与ATF4相互作用，共同调节骨质疏松的病理过程。这些结果表明，ATF4/Nrf2可能是改善骨质疏松的关键治疗靶点，可为OP的治疗提供理论基础。更多还原

【Abstract】 Osteoporosis(OP) is a bone disorder characterized by a decrease in bone density and strength, bone fragility, and an increased risk of fracture. With the coming of aging society, OP and its fracture have become a worldwide public health problem that seriously endangers human health. However, the pathological mechanism of osteoporosis regulation is still unclear. Activation of transcription factor 4(ATF4) is one of the important transcription regulation mitochondria and endoplasmic reticulum stress factor, while the nuclear factor-erythroid 2-related factor 2(Nrf2) is one of the important regulating cell defense of chemical/oxidative stress factor. They play an important role in the process of the pathology of osteoporosis, and it has become a new research hotspot. This review briefly summarizes the pathological significance of ATF4/Nrf2 in the occurrence and development of OP. ATF4 not only plays a key role in Wnt/β-catenin signaling pathway regulating osteoblast formation and differentiation, promoting osteoblast differentiation of bone marrow mesenchymal stem cells, but also promotes osteoblast apoptosis by upregulation of the PERK/eIF2α/CHOP signaling pathway through ER stress. Nrf2, on the other hand, alleviates oxidative damage of osteoblasts mainly by regulating ROS. Meanwhile, Nrf2 can interact with ATF4 to jointly regulate the pathological process of osteoporosis. These results suggest that ATF4/Nrf2may be a key therapeutic target for improving osteoporosis, which may provide a theoretical basis for the treatment of OP.更多还原