High Glucose Inhibits Osteoblst Differentiation of Bone Marrow Stromal Cells by Inducing Ferroptosis
ZHANG Xi, SHAO Gaohai*
This study investigated the effect of high glucose on osteoblast differentiation of BMSCs (bone marrow stroma cells) and its possible mechanism. Using 25.5 mmol/L glucose (HG) to simulate high glucose microenvironment, the level of osteoblast differentiation was detected by ALP (alkaline phosphatase) staining and biochemical quantification. Cell proliferation activity was detected by CCK-8. ROS (reactive oxygen species) was detected by fluorescence probe H2DCFDA and Liperfluo probe was used to detect LPO (lipid peroxidation products), and the mean fluorescence intensity was quantitatively detected by flow cytometry. The expression level of GPX4 (glutathione peroxidase 4) was detected by Western blot. The ultrastructure of mitochondria was observed by TEM (transmission electron microscopy). These results showed that high glucose significantly inhibited osteoblast differentiation and cell proliferation activity of BMSCs, leading to a significant increase in intracellular ROS and LPO levels, while ferroptosis inhibitors could restore osteoblast differentiation and cell proliferation activity of BMSCs, and reduce ROS and LPO levels. In addition, high glucose resulted in mitochondrial shrinkage, smaller volume, increased membrane density, reduced cristae and nucleus. In conclusion, high glucose inhibits osteoblast differentiation of BMSCs by inducing ferroptosis.
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