Biphasic Response to Luteolin in MG-63 Osteoblast-Like Cells under High Glucose‑Induced Oxidative Stress

Background: clinical evidence indicates the diabetes-induced impairment of osteogenesis caused by a decrease in osteoblast activity. flavonoids can increase the differentiation and mineralization of osteoblasts in a high-glucose state. however,some flavonoids such as luteolin may have the potential to induce cytotoxicity in osteoblast-like cells. this study was performed to investigate whether a cytoprotective concentration range of luteolin could be separated from a cytotoxic concentration range in human mg-63 osteoblast-like cells in high-glucose condition.methods: cells were cultured in a normal- or high-glucose medium. cell viability was determined with the mtt assay. the formation of intracellular reactive oxygen species (ros)was measured using probe 2’,7’ -dichlorofluorescein diacetate,and osteogenic differentiation was evaluated with an alkaline phosphatase bioassay.results: ros generation, reduction in alkaline phosphatase activity, and cell death induced by high glucose were inhibited by lower concentrations of luteolin (ec50, 1.29±0.23 μm).oxidative stress mediated by high glucose was also overcome by n-acetyl-l-cysteine. at high concentrations, luteolin caused osteoblast cell death in normal- and high-glucose states (ic50,34±2.33 and 27±2.42 μm, respectively), as represented by increased ros and decreased alkaline phosphatase activity.conclusion: our results indicated that the cytoprotective action of luteolin in glucotoxic condition was manifested in much lower concentrations, by a factor of approximately 26 and 20, than was its cytotoxic activity, which occurred under normal or glucotoxic condition, respectively.