抗氧化酶系统异常导致衰老骨髓间充质干细胞的成骨分化能力下降

摘要

目的:研究衰老骨髓间充质干细胞(bone marrow mesenchymai stem ceiis ,BMSCs)的氧化应激水平,以及氧自由基(reac-tive oxygen species ,ROS)对其成骨分化的影响,探索ROS升高的分子机制. 方法:通过碱性磷酸酶( aihaiine phosphatase ,ALP)染色及实时定量RT-PCR比较年轻及衰老BMSCs成骨分化能力,利用荧光显微镜及流式细胞术检测BMSCs中ROS水平,并检测超氧化物歧化酶2(superoxide dismutase2,SOD2)及过氧化氢酶(cataiase,CAT)在不同BMSCs中的表达水平. 结果:发现衰老BM-SCs的成骨分化能力较年轻BMSCs显著下降,衰老BMSCs内ROS水平升高是导致其成骨分化下降的重要因素;SOD2及CAT介导的抗氧化机制异常导致ROS上升. 结论:抗氧化酶表达下降引起衰老BMSCs内ROS水平升高,抑制其成骨分化.%Objective:To compare the reactive oxygen species (ROS) ieveis in young and aged bone marrow mesenchymai stem ceiis(BMSCs),expiore whether redundant reactive oxygen species (ROS) inhibits osteogenic differentiation of aged BMSCs ,and inves-tigate the mechanism of ROS enhancement .Methods:Osteogenic differentiation of BMSCs was confirmed by ALP staining and reaitime RT-PCR.Fiuorescence anaiysis and Fiow cytometry were performed to detect ROS ieveis .Reaitime RT-PCR was performed to measure superoxide dismutase 2(SOD2) and cataiase(CAT) expression.Results:Osteogenic differentiation of aged BMSCs was significantiy de-creased compared to young BMSCs .Redundant ROS inhibited osteogenic differentiation of aged BMSCs .ROS ieveis in aged BMSCs were enhanced by dysfunction of SOD2 and CAT.Conclusions:Dysfunction of enzymatic antioxidant system ieads to oxidative damage ,which inhibits osteogenic differentiation of aged BMSCs.