文章摘要
胡佳安,吴亚平,陈 忠,黄 蓉,杨建荣,王琰玲,朱玉敏.TAZ激动剂TM⁃25659促进人脂肪干细胞成骨的体内外研究[J].南京医科大学学报,2019,(7):971~977
TAZ激动剂TM⁃25659促进人脂肪干细胞成骨的体内外研究
The TAZ chemical activator TM⁃25659 facilitates osteogenic differentiation of human ADSCs in vitro and in vivo
投稿时间:2018-11-29  
DOI:10.7655/NYDXBNS20190705
中文关键词: 脂肪干细胞  成骨  Hippo通路  TM⁃25659,TAZ
英文关键词: adipose⁃derived stem cells  osteogenesis  Hippo signaling pathway  TM⁃25659  TAZ
基金项目:南京医科大学科技发展基金(2016NJMU058,08NMUM059)
作者单位
胡佳安 南京医科大学口腔疾病研究江苏省重点实验室江苏 南京 210029南京医科大学口腔医学研究所南京医科大学附属口腔医院口腔颌面外科江苏 南京 210029 
吴亚平 南京医科大学口腔疾病研究江苏省重点实验室江苏 南京 210029 
陈 忠 上海健康医学院附属第六人民医院东院(上海市第六人民医院东院)心内科上海 201306 
黄 蓉 南京医科大学口腔疾病研究江苏省重点实验室江苏 南京 210029 
杨建荣 南京医科大学口腔医学研究所南京医科大学附属口腔医院口腔颌面外科江苏 南京 210029 
王琰玲 南京医科大学口腔疾病研究江苏省重点实验室江苏 南京 210029 
朱玉敏 南京医科大学口腔疾病研究江苏省重点实验室江苏 南京 210029 
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中文摘要:
      目的:探索成骨转录共刺激因子TAZ(Tafazzin)激动剂TM?25659对人脂肪干细胞(adipose?derived stem cells,ADSCs)在体内外成骨分化和骨形成过程中的生物学作用。方法:分离培养人ADSCs,通过蛋白质免疫印迹、实时定量PCR检测ADSCs成骨、成脂分化及TM?25659干预后不同时间点TAZ的表达变化,茜素红和油红O染色分别验证其成骨和成脂效果;以β?磷酸三钙(β?tricalcium phosphate,β?TCP)材料为载体负载成骨诱导和TM?25659预处理后的ADSCs植入裸鼠体内,6周后利用苏木精?伊红染色、Masson三色染色和免疫组织化学染色法检测比较ADSCs体内成骨效果。结果:人ADSCs体外成骨分化过程中TAZ表达上调,而在成脂分化中其表达降低。TM?25659促进ADSCs中TAZ的表达,并增强ADSCs体内成骨及骨生成能力。结论:TAZ是促进ADSCs成骨分化的关键调控因子之一,以TAZ为药物靶点可促进ADSCs的骨再生及修复。
英文摘要:
      Objective:The present study aims to determine whether pharmacological activation of the transcriptional coactivator with PDZ?binding motif Tafazzin(TAZ) by chemical TM?25659 can promote osteogenic differentiation and bone formation of adipose?derived stem cells(ADSCs)in vitro and in vivo. Methods:Human ADSCs were isolated and expanded in vitro. The changing expressions of TAZ during ADSCs differentiation at different time points were measured by Western blot and real?time quantitative reverse transcription polymerase chain reaction(PCR). Alizarin red S and oil red O staining were used to detect osteogenic and adipogenic effects. The ADSCs following initial osteogenic differentiation and TM?25659 were loaded on scaffold β?tricalcium phosphate(β?TCP)and then subcutaneously implanted into nude mice. Six weeks later,the results of bone formation in vivo after implantation of the ADSCs were measured and compared by Hematoxylin?Eosin staining,Masson staining and immunohistochemistry staining. Results:TAZ was upregulated during osteogenic differentiation of ADSCs but downregulated during adipogenic differentiation. Pharmacological activation of TAZ by TM?25659 promotes osteogenic differentiation of ADSCs in vitro. The transient treatment of ADSCs with TM?25659 significantly enhances new bone regeneration of ADSCs in vivo. Conclusion:TAZ is a key mediator for promoting osteogenic differentiation of ADSCs. The pharmacological activation of TAZ in ADSCs might become a feasible treatment for bone regeneration and repair.
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