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.

Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

“…In the classical model, Fe 2+ is involved in a variety of biochemical processes within the BCEC, including efflux. There are two storage forms of iron in the cell: stable ferritin and active unbound iron, namely the unstable iron pool (LIP) (Ru et al 2023 ). Excess reactive Fe 2+ as LIP can cause ROS accumulation through Fenton reaction (Yan et al 2021b ).…”

Inhibiting the compensatory elevation of xCT collaborates with disulfiram/copper-induced GSH consumption for cascade ferroptosis and cuproptosis

“…PERK-eIF2α-ATF4 signal pathway was capable of ameliorating ferroptosis by up-regulating HSPA5 and System Xc - [ 35 , 36 ]. On the other hand, erastin-induced ER stress activates the PERK-eIF2α-ATF4-CHOP pathway, leading to an increase in PUMA expression, which participates in the regulation of ferroptosis [ 37 ].…”

G protein-coupled receptor 30 activation inhibits ferroptosis and protects chondrocytes against osteoarthritis

“…Iron overload is common in the tissues of older adults, and ferroptosis plays an important role in the development of chronic diseases. Recent studies have shown that ferroptosis, characterised by the lethal accumulation of reactive iron and lipid peroxide, contributes to degenerative orthopaedic diseases [ 14 ], but ER exerts an anti-ferroptosis effect [ 15 ].…”