Fighting age-related orthopedic diseases: focusing on ferroptosis

Abstract

Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis, particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.

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Funding

National Natural Science Foundation of China (82071970),Science and Technology Innovation Project of Jianghan University (2021kjzx008).

National Natural Science Foundation of China (National Science Foundation of China)(82072506)

National Key R&D Program of China (2019YFA0111900), Provincial Natural Science Foundation of Hunan (2020JJ3060), Provincial Clinical Medical Technology Innovation Project of Hunan (2020SK53709), Innovation-Driven Project of Central South university (2020CX045), Wu Jieping Medical Foundation (320.6750.2020-03-14), CMA▪Young and Middle-aged Doctors Outstanding Development Program--Osteoporosis Specialized Scientific Research Fund Project (G-X-2019-1107-12), the Key program of Health Commission of Hunan Province (20201902)

National Key R&D Program of China (2018YFA0507802)