>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
糖尿病大鼠髌腱来源肌腱干细胞体外成脂分化潜能的实验研究
作者:徐宏亮1 2  石柳3 4 5  李荥娟6  徐林1 2  王宸1 2 3 4  陈辉1 2 3 4  芮云峰1 2 3 4 
单位:1. 无锡市锡山人民医院 骨科, 江苏 无锡 214000;
2. 东南大学附属中大医院无锡分院 骨科, 江苏 无锡 214000;
3. 东南大学附属中大医院 骨科, 江苏 南京 210009;
4. 东南大学 创伤骨科研究所, 江苏 南京 210009;
5. 香港中文大学 矫形外科及创伤学系, 香港;
6.
关键词:糖尿病 髌腱 肌腱干细胞 成脂分化 大鼠 
分类号:R-33;R587.1
出版年·卷·期(页码):2018·37·第三期(390-395)
摘要:

目的:观察糖尿病大鼠髌腱来源的肌腱干细胞(TDSCs)体外成脂分化的潜能,探讨糖尿病对TDSCs成脂分化潜能的影响。方法:采用链脲佐菌素建立糖尿病大鼠模型,提取大鼠髌腱TDSCs;观察细胞形态,并在体外诱导其成脂分化,通过油红O染色和检测成脂分化相关基因(C/EBP和PPARγ2)的mRNA表达,比较糖尿病组与对照组TDSCs成脂分化潜能的差异。结果:造模后糖尿病组血糖水平显著高于对照组,并持续高于250 mg·dl-1。对照组TDSCs (hTDSCs)形态在镜下表现为均一的细长纺锤型,而糖尿病组TDSCs (dTDSCs)表现为多突的纺锤型。成脂分化诱导9 d后,经油红O染色,对照组细胞内可见大量的脂滴形成,而糖尿病组细胞内仅有少量的脂滴形成,dTDSCs油红O染色阳性率显著低于对照组。dTDSCs C/EBP、PPARγ2的mRNA水平也显著低于hTDSCs。结论:糖尿病TDSCs体外成脂分化能力较hTDSCs显著降低,此结果为进一步揭示糖尿病肌腱病变过程中,持续体内高糖环境对TDSCs成脂分化功能影响的潜在分子机制提供了细胞生物学依据。

Objective: To investigate the adipogenic differentiation potential of tendon-derived stem cells(TDSCs) in diabetes mellitus rats.Methods: The diabetic rats were induced by streptozotocin and the TDSCs were isolated at week 2 post induction. The morphology of both healthy TDSCs(hTDSCs) and diabetic TDSCs(dTDSCs) was photographed under light microscopy. Oil Red O staining and C/EBP and PPARγ2 expression level were measured by qRT-PCR at day 9 post adipogenic induction.Results: Blood glucose levels of diabetic rats were sustained higher than 250 mg·dl-1 after STZ injection. Both kinds of the TDSCs presented the slender spindle shaped morphology while there was a little change in dTDSCs. Significantly decreased oil red O-positive droplets in dTDSCs than hTDSCs were discovered. qRT-PCR results also indicated that the mRNA expressions of C/EBP and PPARγ2 in the TDSCs from the diabetic tendons were higher than those in hTDSCs.Conclusion: TDSCs from STZ induced diabetic rats show more significantly decreased adipogenic differentiation potential than those from healthy controls, which might contribute to better understanding of the pathogenesis of diabetic tendinopathy.

参考文献:

[1] WONG J,CONSTANTINO M,YUE D K.Morbidity and mortality in young-onset type 2 diabetes in comparison to type 1 diabetes:where are we now?[J].Curr Diab Rep,2015,15(1):566.
[2] SHI L,RUI Y F,LI G,et al.Alterations of tendons in diabetes mellitus:what are the current findings?[J].Int Orthop,2015,39(8):1465-1473.
[3] RUI Y F,LUI P P,LI G,et al.Isolation and characterization of multipotent rat tendon-derived stem cells[J].Tissue Eng Part A,2010,16(5):1549-1558.
[4] FOX A J,BEDI A,DENG X H,et al.Diabetes mellitus alters the mechanical properties of the native tendon in an experimental rat model[J].J Orthop Res,2011,29(6):880-885.
[5] SZKUDELSKI T.The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas[J].Physiol Res,2001,50(6):537-546.
[6] RUI Y F,LUI P P,WONG Y M,et al.Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy[J].Stem Cells Dev,2013,22(7):1076-1085.
[7] RAMIREZ-ZACARIAS J L,CASTRO-MUNOZLEDO F,KURI-HARCUCH W.Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O[J].Histochemistry,1992,97(6):493-497.
[8] de OLIVEIRA R R,de LIRA K D,SILVEIRA P V,et al.Mechanical properties of achilles tendon in rats induced to experimental diabetes[J].Ann Biomed Eng,2011,39(5):1528-1534.
[9] COOKE D W,PLOTNICK L.Type 1 diabetes mellitus in pediatrics[J].Pediatr Rev,2008,29(11):374-384,385.
[10] CRISTANCHO A G,LAZAR M A.Forming functional fat:a growing understanding of adipocyte differentiation[J].Nat Rev Mol Cell Biol,2011,12(11):722-734.
[11] NADLER S T,STOEHR J P,SCHUELER K L,et al.The expression of adipogenic genes is decreased in obesity and diabetes mellitus[J].Proc Natl Acad Sci U S A,2000,97(21):11371-11376.
[12] LIN Y C,LI Y J,RUI Y F,et al.The effects of high glucose on tendon-derived stem cells:implications of the pathogenesis of diabetic tendon disorders[J].Oncotarget,2017,8(11):17518-17528.
[13] KLEMM D J,LEITNER J W,WATSON P,et al.Insulin-induced adipocyte differentiation.Activation of CREB rescues adipogenesis from the arrest caused by inhibition of prenylation[J].J Biol Chem,2001,276(30):28430-28435.
[14] LEHNER C,GEHWOLF R,WAGNER A,et al.Tendons from non-diabetic humans and rats harbor a population of insulin-producing,pancreatic beta cell-like cells[J].Horm Metab Res,2012,44(7):506-510.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 412717 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364