Deer antler peptide modulation of the SLC7A11/GPX4 axis inhibits dexamethasone-induced ferroptosis in osteoblasts
BACKGROUND:Steroid-induced osteonecrosis of the femoral head is closely related to ferroptosis in osteoblasts.Deer antler peptide can promote the survival and functional establishment of osteoclasts by inhibiting ferroptosis in osteoblasts,and has the potential to treat steroid-induced osteonecrosis of the femoral head,but its regulatory mechanism of ferroptosis in osteoblasts has not yet been clarified.OBJECTIVE:To investigate the mechanism by which deer antler peptide inhibits dexamethasone-induced ferroptosis in osteoblasts.METHODS:(1)Different concentration gradients of antler peptide and dexamethasone were used to intervene in MC3T3-E1 14 cells,and the cell activity was detected by cell counting kit-8 method to determine the effect concentration of antler peptide and dexamethasone.(2)MC3T3-E1 14 cells treated with dexamethasone(800 μmol/L)were intervened with different concentrations of gradient antler polypeptide,which were then divided into blank control group,dexamethasone group and dexamethasone+antler peptide group.Cell counting kit-8 method was used to calculate the effects of different concentrations of antler polypeptide on the proliferation of MC3T3-E1 14 cells.(3)Glutathione,superoxide dismutase,malondialdehyde,lipid peroxide,cellular iron,and reactive oxygen species levels in the blank control group,dexamethasone group and dexamethasone+antler peptide group were detected using kits.The protein expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 were detected by western blot to verify the pathway by which antler polypeptide inhibits ferroptosis.RESULTS AND CONCIUSION:After cell activity was detected by cell counting kit-8 assay,antler peptide(10 mg/mL)and dexamethasone(800 μmol/L)were selected to treat MC3T3-E1 14 cells for 24 hours in subsequent experiments.After treatment with dexamethasone,malondialdehyde,lipid peroxide,cellular iron and reactive oxygen species levels were all increased(P<0.01),while glutathione content and superoxide dismutase activity were decreased and the protein expression of glutathione peroxidase 4 and solute carrier family 7 member 11 were also decreased(P<0.05-0.01).After antler peptide intervention,the changes in the above indexes were obviously reversed(P<0.05-0.01).To conclude,antler peptide may inhibit ferroptosis in osteoblasts by regulating the glutathione peroxidase 4/solute carrier family 7 member 11 axis,and thereby exert a therapeutic role in steroid-induced osteonecrosis of the femoral head.
antler peptidedexamethasonesteroid-induced osteonecrosis of the femoral headinhibitionosteoblastferroptosis
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