The role of extracellular vesicles in iron homeostasis and ferroptosis: Focus on musculoskeletal diseases

Abstract

Iron homeostasis is crucial for maintaining proper cellular function, and its disruption is considered one of the pathogenic mechanisms underlying musculoskeletal diseases. Under conditions of oxidative stress, the accumulation of cellular iron overload and lipid peroxidation can lead to ferroptosis. Extracellular vesicles (EVs), serving as mediators in the cell‐to‐cell communication, play an important role in regulating the outcome of cell ferroptosis. Growing evidence has proven that EV biogenesis and secretion are tightly associated with cellular iron export. Furthermore, different sources of EVs deliver diverse cargoes to bring about phenotypic changes in the recipient cells, either activating or inhibiting ferroptosis. Thus, delivering therapies targeting ferroptosis through EVs may hold significant potential for treating musculoskeletal diseases. This review aims to summarize current knowledge on the role of EVs in iron homeostasis and ferroptosis, as well as their therapeutic applications in musculoskeletal diseases, and thereby provide valuable insights for both research and clinical practice.

Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading

“…Brent R. Stockwell identified metabolism, ROS, and iron biology as pivotal regulators of ferroptosis [8] . Moreover, a plethora of studies have also demonstrated that intracellular iron-loading status is necessary for intracellular ferroptosis [ 9 , 10 ]. Furthermore, it has been discovered that intracellular iron overload, which is mediated by hepcidin and ferroportin (FPN1), is the key link to the occurrence of ferroptosis [ 8 , 11 ].…”

Enrichment of Bioactive Lipids in Urinary Extracellular Vesicles and Evidence of Apoptosis in Kidneys of Hypertensive Diabetic Cathepsin B Knockout Mice after Streptozotocin Treatment

“…Apoptosis is a form of programmed cell death mediated by extrinsic or intrinsic pathways that allow for the removal of damaged cells [10]. The biogenesis and release of EVs have been shown to be associated with the export of cellular iron [11]. Wu et al identified multiple ferroptosis-related genes in syncytiotrophoblast-derived EVs [12].…”