Li Chenchen, Gong He, Zhang Yingying, Shi Peipei, Liu Shuyu, Zhang Qi
Medical Engineering & Engineering Medicine Innovation Center, Hangzhou International Innovation Institute, Beihang University, Hangzhou, China.
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
FASEB J. 2025 Jun 30;39(12):e70769. doi: 10.1096/fj.202500415R.
Diabetic osteoporosis (DOP), as a metabolic bone disease, leads to an increased risk of fracture in patients and imposes a huge burden on society and individuals. The microenvironment of type two diabetes mellitus (T2DM) may contribute to osteoporosis by triggering cell death in bone tissue. Ferroptosis is a novel type of regulated cell death driven by iron-dependent lipid peroxidation discovered in recent years, and the main molecular mechanism involves dysregulation of iron homeostasis, mitochondrial dysfunction, impaired antioxidant capacity, and accumulation of lipid peroxides. In recent years, there has been increasing evidence that ferroptosis is involved in the pathophysiologic process of DOP. However, its exact role and potential molecular mechanisms have not been fully elucidated. In this paper, the role of ferroptosis in developing T2DM and osteoporosis is reviewed, with the intention of providing novel insights into the pathophysiologic investigation of DOP. Furthermore, possible therapeutic compounds that target the ferroptosis signaling system are presented, and ways for leveraging ferroptosis in the prevention and treatment of DOP are examined. These findings are anticipated to offer new directions for the therapeutic intervention and drug development for DOP.
糖尿病性骨质疏松症（DOP）作为一种代谢性骨病，会增加患者骨折的风险，给社会和个人带来巨大负担。2型糖尿病（T2DM）的微环境可能通过引发骨组织细胞死亡而导致骨质疏松症。铁死亡是近年来发现的一种由铁依赖性脂质过氧化驱动的新型程序性细胞死亡，其主要分子机制涉及铁稳态失调、线粒体功能障碍、抗氧化能力受损以及脂质过氧化物的积累。近年来，越来越多的证据表明铁死亡参与了DOP的病理生理过程。然而，其确切作用和潜在分子机制尚未完全阐明。本文综述了铁死亡在T2DM和骨质疏松症发生发展中的作用，旨在为DOP的病理生理研究提供新的见解。此外，还介绍了针对铁死亡信号系统的可能治疗化合物，并探讨了利用铁死亡预防和治疗DOP的方法。这些发现有望为DOP的治疗干预和药物开发提供新的方向。
