中国免疫学杂志2024，Vol.40Issue(8)：1625-1633,9.DOI:10.3969/j.issn.1000-484X.2024.08.010
微重力介导Notch1信号通路调控巨噬细胞极化影响骨稳态
Microgravity-mediated Notch1 signaling pathway affects bone homeostasis by regulating macrophage polarization
摘要
Abstract
Objective:To investigate the effect of microgravity-mediated Notch1 signaling on macrophage polarization on bone homeostasis.Methods:The animal model was constructed by tail-limb suspension(HLS)to simulate the microgravity environment.The animals were grouped into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.ELISA was used to detect the content of TNF-α and IL-1β in serum of rats.TUNEL staining was used to detect the apoptosis of bone tissue.Immunofluo-rescence was used to detect the polarization of macrophages in bone tissue.The rat osteoblast CP-R091 microgravity model was con-structed by simulating the microgravity environment with a rotating wall bioreactor.The cell experiments were divided into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.CCK-8 test was used to detect the proliferation activity of cells in each group,and AO test was used to test the apoptosis rate of cells in each group.PCR was used to detect the expression of os-teogenesis-related genes in bone tissues and cells.Western blot was used to detect the expression of Notch1,hair division-related en-hancer-1(HES-1),and Notch pathway ligand 1(Jagged1)in bone tissues and cells of each group.Results:Compared with control group,the contents of TNF-α and IL-1β in the serum of the rats in the HLS group,the apoptosis rate,and the proportion of M1 macro-phages were significantly increased.Compared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while HLS+rhNF-κB group significantly changed the above parameter values.Compared with control group,the proliferation activity of the cells in the HLS group was significantly reduced,and the apoptosis rate was significantly increased.Com-pared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while the HLS+rhNF-κB group made the above parameter values worse.The expressions of the osteogenesis-related genes collagen type Ⅰ(COL1),osteocalcin(OCN)and Runt-related transcription factor 2(RUNX2)in bone tissues and cells in the microgravity environment were significantly decreased,while the expressions of Notch-1,Hes-1 and Jagged1 were significantly increased,and the differences were statistically significant(all P<0.05).Conclusion:Microgravity-mediated Notch1 signaling regulates M1/M2 polarization of macro-phages,participates in cell proliferation and apoptosis in bone tissue,and affects the progress of bone homeostasis.关键词
微重力/果蝇双翅边缘缺刻同源基因1/巨噬细胞极化/骨稳态Key words
Microgravity/Notch-1/Macrophage polarization/Bone homeostasis分类
医药卫生引用本文复制引用
许静,郭健,罗永贵,李大星,唐英,娄宝佳,彭淼,郑永..微重力介导Notch1信号通路调控巨噬细胞极化影响骨稳态[J].中国免疫学杂志,2024,40(8):1625-1633,9.基金项目
贵州省卫生健康委员会项目(gzwkj2022-033). （gzwkj2022-033）
