Deferoxamine alleviates the inhibitory effect of glucocorticoids on osteogenic differentiation

doi:10.12307/2026.525

Abstract

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.

Key words: MC3T3-E1 cells, osteonecrosis of the femoral head, osteogenic differentiation, glucocorticoids, hypoxia-inducible factor 1α, vascular endothelial growth factor, deferoxamine

CLC Number:

Tang Haoxu, Liang Yingjie, Li Ce, Ding Penglin, Qian Minlong, Yuan Lingli. Deferoxamine alleviates the inhibitory effect of glucocorticoids on osteogenic differentiation[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(32): 6821-6827.

Figures/Tables 6

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