丙酰肉碱调控xCT/GPX4铁死亡途径并缓解骨质疏松症进展OA

Objective:To investigate the potential mechanism of propionylcarnitine in regulating xCT/GPX4 ferroptosis path-way and improving osteoporosis,and to reveal its dual role in the regulation of ferroptosis and osteogenic activity.Methods:The effect of propionylcarnitine on ferroptosis pathway and osteogenesis-related protein expression in pre-osteoblasts MC3T3-E1 was investigated.MC3T3-E1 was pretreated with ferroptosis agonist,and after treatment with propionylcarnitine and ferroptosis inhibi-tors,ROS immunofluorescence staining,MDA detection,mitochondrial transmission electron microscopy and Western blot were used to detect ferroptosis-related indexes of cells.The expression of osteogenesis-related proteins was detected by alkaline phos-phatase staining,alizarin red staining and Western blot.An osteoporosis model of bilateral oophorectomy(OVX)in SD rats was constructed,treated with propionylcarnitine,and femur tissue samples were collected three months later,and the changes of bone density,trabecular bone and other parameters in the tissue samples were analyzed by Micro-CT scanning and tissue H&E staining.Results:The results of cell experiments showed that the expression level of anti-ferroptosis-related proteins(GPX4/xCT)in MC3T3-E1 cells was significantly increased after ferroptosis inhibitor or propionylcarnitine treatment,and the mitochondrial mor-phology in cells was improved.In addition,alkaline phosphatase activity,calcium deposition and osteogenesis-related protein ex-pression were also significantly increased in these two groups.The results of micro-CT of the femur of rats showed that the trabec-ular bone density and trabecular number in the bone tissue of the propionylcarnitine treatment group increased compared to the OVX model group.H&E staining showed that the trabecular bone thickness in the propionylcarnitine treatment group was signifi-cantly higher than that in the OVX model group.Conclusion:Propionylcarnitine can reduce ferroptosis induced by ferroptosis ago-nist,up-regulate osteogenic activity,and improve the progression of osteoporosis in OVX rats.