南方医科大学学报2024，Vol.44Issue(7)：1227-1235,9.DOI:10.12122/j.issn.1673-4254.2024.07.02
抑制Hmga2促进小鼠脂肪间充质干细胞成骨分化并加速骨缺损修复
Hmga2 knockdown enhances osteogenic differentiation of adipose-derived mesenchymal stem cells and accelerates bone defect healing in mice
摘要
Abstract
Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.关键词
脂肪间充质干细胞/高迁移率族蛋白A2/成骨分化/骨缺损修复Key words
adipose-derived mesenchymal stem cells/high-mobility group AT-hook 2/osteogenic differentiation/bone defect healing引用本文复制引用
柯志勇,黄子城,何若琳,张倩,陈思旭,崔忠凯,丁晶..抑制Hmga2促进小鼠脂肪间充质干细胞成骨分化并加速骨缺损修复[J].南方医科大学学报,2024,44(7):1227-1235,9.基金项目
国家自然科学基金(32270792) （32270792）
上海交通大学医工交叉"多学科交叉项目培育(转化)"(YQ2021QN48) Supported by National Natural Science Foundation of China(32270792). （转化）
