Targeting Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review.

Skeletal system diseases, encompassing chronic disorders of the skeletal system which commonly include osteoarthritis, rheumatoid arthritis, osteoporosis and osteosarcoma. Their incidence rates have been increasing in recent years, resulting in significant social and economic burdens. However, their pathogenesis remains inadequately explored. Ferroptosis, a recently identified form of regulated cell death, differs from other cell death mechanisms, such as apoptosis and autophagy, by primarily involving iron metabolism and lipid peroxidation. The underlying mechanism of ferroptosis is characterised by intracellular iron overload and accumulation of ROS, both of which contribute to the onset of osteoarthritis, rheumatoid arthritis and osteoporosis and are closely linked to the malignancy of osteosarcoma. To enhance understanding of ferroptosis' potential role in the pathophysiology and treatment of skeletal system diseases, this review examines its relationship with these conditions, the mechanisms involved and the therapeutic potential of natural compounds in modulating ferroptosis. By investigating the contribution of ferroptosis to the occurrence and progression of these diseases, novel clinical targets for diagnosis and treatment are proposed.