Protective Effects and Mechanisms of Quercetin on Osteoporotic Rats via Modulating the Ferroptosis Pathway

Abstract

Background & aims: Osteoporosis, a widespread bone disorder primarily affecting postmenopausal women, poses a significant public health challenge. Recent research has linked ferroptosis to the development of osteoporosis. This study explored the possible anti-osteoporosis benefits of quercetin. Additionally, the underlying mechanisms were studied, with a special emphasis on the modulation of ferroptosis. Method: In this study, ovariectomy (OVX)-induced osteoporotic rats were employed. They were subjected to treatment with Quercetin and Deferoxamine (DFO, a ferroptosis inhibitor) to investigate the therapeutic effects of Quercetin and ferroptosis inhibition on osteoporosis. Various parameters were assessed, including the morphological characteristics of femoral bone tissue and bone quality (femoral bone mineral density and bone mineral salt content). To evaluate the influence of Quercetin on ferroptosis, hepatic iron deposition, apoptosis rates of bone tissue cells and the expression levels of ferroptosis-associated proteins Xc-cystine (xCT), Voltage-Dependent Anion-Selective Channel Protein 2 (VDAC2), transferrin receptor 1 (TFR1), and glutathione peroxidase 4 (GPX4) were quantified. Results: In ovariectomized rats, we found a significant decrease in bone mineral density and impaired morphological characteristics of femoral bone tissue, which is typical of osteoporosis (p < 0.05). Notably, quercetin therapy effectively ameliorated these negative effects and increased bone health in the osteoporotic rat model (p < 0.05). The ferroptosis pathway was significantly suppressed by quercetin administration, evidenced by altered expression levels of key ferroptosis-related components such as GPX4 and transferrin receptor 1 (TFR1) (p < 0.05). Conclusion: Quercetin suppresses ferroptosis, which contributes to enhanced bone density and bone mineral content in ovariectomized rats. It additionally corresponds to a decrease in bone turnover, indicating that it might address bone-related disorders.