Targeting oxidative stress, iron overload and ferroptosis in bone-degenerative conditions

Abstract

Abstract Introduction Bone-degenerative conditions, including osteoporosis, rheumatoid arthritis, and osteoarthritis, are major public health concerns worldwide, associated with oxidative stress and iron overload that disrupts bone homeostasis. Ferroptosis, an iron-mediated form of cell death, has emerged as a critical factor in bone degeneration, necessitating a comprehensive review of its role in these conditions. Content This review comprehensively examined the latest research on oxidative stress, iron metabolism, and ferroptosis related to bone biology and degeneration, focusing on their interconnections and potential therapeutic implications. The review revealed that oxidative stress affects various bone cell types, including osteoclasts, osteoblasts, and chondrocytes, contributing to bone loss and cartilage degradation. Iron homeostasis was found to be crucial for bone cell function, with both iron overload and deficiency potentially leading to pathological conditions. Ferroptosis regulation involves a complex interplay between iron metabolism, lipid peroxidation, and antioxidant systems, including the SLC7A11-GSH-GPX4 network and the FSP1-CoQ10H2 pathway. Different bone cell lineages, including mesenchymal stem cells, osteoblasts, osteoclasts, and chondrocytes, exhibit varied responses to ferroptosis induction and regulation. Summary Understanding the molecular mechanisms underlying ferroptosis regulation in bone cells offers promising avenues for developing targeted therapies for bone-degenerative conditions. Outlook Future research should focus on elucidating the specific roles of ferroptosis in different bone disorders and exploring potential therapeutic interventions targeting oxidative stress, iron overload, and ferroptosis pathways to improve the management of these debilitating conditions.