Deferoxamine alleviates the inhibitory effect of glucocorticoids on osteogenic differentiation

Tang Haoxu; Liang Yingjie; Li Ce; Ding Penglin; Qian Minlong; Yuan Lingli

doi:10.12307/2026.525

Abstract：BACKGROUND:Deferoxamine exhibits multiple functions such as stem cell modulation,immune regulation,and promotion of angiogenesis and osteogenesis,but its role in the osteoinhibition induced by dexamethasone in osteoblasts remains unclear. OBJECTIVE:To investigate the effects of deferoxamine on osteoblasts treated with dexamethasone through the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway and to explore its potential mechanisms of action. METHODS:The proliferation of MC3T3-E1 cells treated with various concentrations of deferoxamine for 24,48,and 72 hours was assessed using the cell counting kit-8 assay to determine the optimal intervention concentration.There were control,dexamethasone,dexamethasone plus deferoxamine 10 μmol/L,and dexamethasone plus deferoxamine 20 μmol/L groups in the experiment.Cell counting kit-8 assay and flow cytometry were employed to evaluate the effect of deferoxamine on dexamethasone-induced cell proliferation and apoptosis.Alkaline phosphatase staining and activity assays were conducted to assess alkaline phosphatase levels in MC3T3-E1 cells.Alizarin red staining was used to observe the formation of mineralized nodules.Western blot was employed to detect the expression of osteogenic and signaling proteins. RESULTS AND CONCLUSION:(1)Deferoxamine showed no significant cytotoxicity to MC3T3-E1 cells within the range of 5-20 μmol/L and could ameliorate the inhibitory effects of dexamethasone on MC3T3-E1 cell proliferation and apoptosis.(2)Compared with the dexamethasone group,deferoxamine groups increased alkaline phosphatase activity and cell mineralization,and also significantly increased the protein expression of osteopontin,runt-related transcription factor 2,and alkaline phosphatase in MC3T3-E1 cells.(3)Deferoxamine also activated the hypoxia-inducible factor 1α/vascular endothelial growth factor pathway in dexamethasone-treated MC3T3-E1 cells.To conclude,deferoxamine can alleviate apoptosis in osteoblasts induced by dexamethasone treatment,maintain the vitality of osteoblasts by activating the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway,and promote their proliferation,which may help delay the progression of steroid-induced osteonecrosis of the femoral head.