Ferroptosis: A New Regulatory Mechanism in Osteoporosis

Abstract

Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and immune regulation. Studies using animal models of osteoporosis in vivo and cell models in vitro will help clarify the relationship between ferroptosis and osteoporosis and provide research ideas for the elucidation of new mechanisms and development of new technologies and new drugs for the treatment of osteoporosis in the future.

Maresin1 Suppresses High-Glucose-Induced Ferroptosis in Osteoblasts via NRF2 Activation in Type 2 Diabetic Osteoporosis

“…Among the downstream target molecules of NRF2, we found that GPX4 and SLC7A11 are essential markers of ferroptosis as well. An increasing number of studies have recently revealed that ferroptosis is involved in the mechanisms underlying diabetic osteogenesis [ 65 ]. As a pattern of regulated cell death, ferroptosis is distinguished by intracellular iron overload and lipid ROS accumulation [ 66 ].…”

Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives

“…Prednisolone induces osteoblasts and osteocytes apoptosis leading to a reduction in bone formation [ 30 ]. It is well known that iron is an important risk factor for OP [ 31 , 32 ]. Iron overload can influence bone formation and remodeling affecting bone microarchitecture and inducing bone loss [ 33 , 34 ].…”

Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases

“…With intramuscular injection of lentivirus expressing TFR1, skeletal muscle regeneration is enhanced and suppresses ferroptosis in different age groups of mice, thus preventing osteoporosis [ 91 ]. Liu et al further clarified the relationship between ferroptosis and osteoporosis through animal models of osteoporosis in vivo and cell models in vitro [ 92 ]. From the above research content, we have a better understanding of ferroptosis orchestrated with osteoporosis than before and can treat and prevent osteoporosis according to some targets.…”