Exosomes derived from vascular endothelial cells antagonize glucocorticoid‐induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts

Abstract

High dose and long‐term steroid treatment can alter antioxidative ability and decrease the viability and function of osteoblasts, leading to osteoporosis and osteonecrosis. Ferroptosis, a new type of cell death characterized by excessive lipid peroxidation due to the downregulation of GPX4 and system X^c−, is involved in glucocorticoid‐induced osteoporosis. Endothelial cell‐secreted exosomes (EC‐Exos) are important mediators of cell‐to‐cell communication and are involved in many physiological and pathological processes. However, the effect of EC‐Exos on osteoblasts exposed to glucocorticoids has not been reported. Here, we explored the role of EC‐Exos in glucocorticoid‐induced osteoporosis. In vivo and in vitro experiments indicated that EC‐Exos reversed the glucocorticoid‐induced osteogenic inhibition of osteoblasts by inhibiting ferritinophagy‐dependent ferroptosis.