华西口腔医学杂志2025,Vol.43Issue(4):559-569,11.DOI:10.7518/hxkq.2025.2024468
柚皮素调控叉头转录因子1/β-连环蛋白通路对过氧化氢诱导的人牙周膜干细胞氧化损伤的保护作用研究
Investigating the protective effect of naringenin on hydrogen peroxide induced oxidative damage of human periodontal ligament stem cells by regulating the forkhead box protein O-1/β-catenin pathway
摘要
Abstract
Objective Investigating the protective effect of naringenin(NAR)on the osteogenic potential of hu-man periodontal ligament stem cells(hPDLSCs)under oxidative stress and its related mechanisms.Methods The oxidative damage model of hPDLSCs was estab-lished using hydrogen peroxide(H2O2)and the hPDLSCs were treated with different concentrations of NAR and 0.5 μmol/L forkhead box protein O-1(FOXO1)inhibitor AS1842856.After that,the cell counting kit-8(CCK8)was used to determine the optimal concentrations of H2O2 and NAR.The alkaline phosphatase(ALP)staining and real time fluo-rescent quantitative reverse transcription polymerase chain reaction(qRT-PCR)were employed to assess the expression of ALP,runt-related transcription factor 2(RUNX2)and osteocalcin(OCN)in hPDLSCs of each group.The enzyme-linked immunosorbent assay(ELISA)and 2',7'-dichlorofluorescin diacetate(DCFH-DA)staining were utilized to evalu-ate the expression of reactive oxygen species(ROS),malondialdehyde(MDA)and lactate dehydrogenase(LDH)in hP-DLSCs.Meanwhile,qRT-PCR and western blot were used to detect the expression levels of FOXO1 and β-catenin,both are pathway related genes and proteins.Results H2O2 exposure led to an increase in oxidative damage in hPDLSCs,characterized by a rise in intracellular ROS levels and increased expression of MDA and LDH(P<0.05).At the same time,the osteogenic differentiation ability of hPDLSCs decreased,as evidenced by lighter ALP staining and reduced ex-pression levels of osteogenic differentiation-related genes ALP,RUNX2 and OCN(P<0.05).Co-treatment with NAR al-leviated the oxidative damage in hPDLSCs,enhanced their antioxidant capacity,and restored their osteogenic ability.The FOXO1 inhibitor AS 1842856 downregulated the expression of β-catenin(P<0.05)and significantly diminished both the antioxidant effect of NAR and its ability to restore osteogenesis(P<0.05).Conclusion NAR can enhance the antioxi-dant capacity of hPDLSCs by activating the FOXO1/β-catenin signaling pathway within hPDLSCs,thereby mitigating oxidative stress damage and alleviating the loss of osteogenic capacity.关键词
牙周膜干细胞/叉头转录因子1/β-连环蛋白信号通路/氧化应激/柚皮素/成骨分化Key words
periodontal ligament stem cells/forkhead box protein O-1/β-catenin signaling pathway/oxidative stress/naringenin/osteogenic differentiation分类
医药卫生引用本文复制引用
张丽,彭世元,唐飞扬,蹇静薇,袁硕声,徐晓梅..柚皮素调控叉头转录因子1/β-连环蛋白通路对过氧化氢诱导的人牙周膜干细胞氧化损伤的保护作用研究[J].华西口腔医学杂志,2025,43(4):559-569,11.基金项目
Sichuan Science and Technology Program(2023ZYD0112) (2023ZYD0112)
College Student Innovation and Entrepreneur-ship Project(2023463) (2023463)
Luzhou Science and Technology Program(2024LZXNYDJ041) 四川省科技计划项目(2023ZYD0112) (2024LZXNYDJ041)
大学生创新创业项目(2023463) (2023463)
泸州市科技计划项目(2024LZXNYDJ041) (2024LZXNYDJ041)