维生素 D3 减轻高糖暴露诱导氧化应激促进人脐带间充质干细胞的成骨分化.

BACKGROUND: Diabetic osteoporosis is gaining public attention. However, few studies have reported the effect of a high-glucose environment on the osteogenic differentiation of human umbilical cord mesenchymal stem cells and the corresponding therapeutic strategies. OBJECTIVE: To investigate whether vitamin D3 can restore the osteogenic differentiation potential of human umbilical cord mesenchymal stem cells in a high)glucose environment. METHODS: The viability of human umbilical cord mesenchymal stem cells was detected by CCK-8 assay to screen the appropriate vitamin D3 intervention concentration. Under the high-glucose environment, RT-qPCR, western blot assay, immunofluorescence, JC-1 mitochondrial membrane potential, alizarin red staining, and β-galactosidase staining were used to evaluate the osteogenic differentiation potential, intracellular reactive oxygen species accumulation, mitochondrial membrane potential alteration, and cell senescence of human umbilical cord mesenchymal stem cells after vitamin D3 intervention. The underlying mechanism was also discussed. RESULTS AND CONCLUSION: (1) Vitamin D3 significantly promoted the proliferation of human umbilical cord mesenchymal stem cells in the range of 0.1 μmol/L to 1 mmol/L. (2) High-glucose environment down-regulated the mRNA and protein level expressions of osteogenic-related genes α1-I collagen, alkaline phosphatase, Runt-associated transcription factor 2, and osteocalcin in human umbilical cord mesenchymal stem cells, which induced oxidative stress and cellular senescence. (3) Vitamin D3 at an intervention concentration of 10 μmol/L significantly restored the osteogenic phenotype of human umbilical cord mesenchymal stem cells under high-glucose conditions and attenuated intracellular oxidative stress and cellular senescence by activating the Nrf2/HO-1 signaling pathway. (4) These findings suggested that the osteogenic differentiation ability of human umbilical cord mesenchymal stem cells was reduced in the high-glucose environment, and vitamin D3 could partially improve their osteogenic differentiation ability and reduce cell damage. [ABSTRACT FROM AUTHOR]