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.
Highlights
Cell death includes apoptosis, pyroptosis, necrosis, autophagy, ferroptosis, and other death mechanisms
We summarize the relationship between ferroptosis and osteoporosis and show how ferroptosis regulates diabetic osteoporosis (DOP), glucocorticoidinduced osteoporosis (GIOP), and postmenopausal osteoporosis (PMOP)
Liu et al found the ironstarvation response and ferritinophagy under normoxia in the process of osteoclast differentiation confirmed the involvement of ferroptosis; following receptor activator of nuclear factor-kappa B ligand (RANKL) stimulation, MDA and prostaglandin endoperoxide synthase 2 (PTGS2) gene expression in bone marrow-derived macrophages (BMDMs) were increased, GSH and iron levels in the culture medium supernatant decreased, and iron accumulation in mitochondria was observed [76]
Summary
Pyroptosis, necrosis, autophagy, ferroptosis, and other death mechanisms. Before the concept of ferroptosis was revealed, one study showed that the regulation of iron metabolism and the maintenance of iron homeostasis have indispensable biological roles in the human pathophysiological process. In 2003, Dolma et al [1] found that the small molecule erastin can induce RAS mutations in tumor cells, leading to cell death in a manner different from traditional apoptosis. In 2008, using highthroughput small-molecule screening technology, it was found that Ras selective lethal small molecules could kill human foreskin fibroblasts (BJeLR) in a nonapoptotic manner [2]; neither apoptosis inhibitors nor necrostatin inhibitors (Necrostatin-1) [3] could reverse cell death induced by erastin and RSLs. In contrast, the antioxidant vitamin E and the iron-chelating agent deferoxamine mesylate (DFO) can inhibit cell death [4], indicating that ferroptosis is an iron-dependent cell death process. We summarize the relationship between ferroptosis and osteoporosis and show how ferroptosis regulates diabetic osteoporosis (DOP), glucocorticoidinduced osteoporosis (GIOP), and postmenopausal osteoporosis (PMOP)
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