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

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 Xc-, 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.

Automated summary

High dose and long-term steroid treatment can lead to osteoporosis and osteonecrosis by altering antioxidative ability and inducing excessive lipid peroxidation through pathways like ferroptosis. Endothelial cell-secreted exosomes play a protective role in glucocorticoid-induced osteoporosis by inhibiting ferroptosis-dependent osteogenic inhibition of osteoblasts.