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The promotion of bone regeneration through CS/GP-CTH/antagomir-133a/b sustained release system.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-10-28 , DOI: 10.1016/j.nano.2019.102116
Fusong Jiang 1 , Fuli Yin 2 , Yiwei Lin 2 , Wenyang Xia 2 , Lihui Zhou 3 , Chenhao Pan 2 , Nan Wang 4 , Haojie Shan 2 , Zubin Zhou 2 , Xiaowei Yu 2
Affiliation  

Few studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via antagomiR-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-antagomiR-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can facilitate continuous dosing of antagomiR-133a/b, which enhanced calcium deposition and osteogenic specific gene expression in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-antagomiR-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of antagomiR133a/b, which can promote osteogenic differentiation.

中文翻译:

通过CS / GP-CTH / antagomir-133a / b持续释放系统促进骨骼再生。

很少有研究报道miRNA在骨骼再生中的应用。在这项研究中,通过antagomiR-133a / b抑制了鼠BMSCs中miR133a和miR133b的表达,并评估了鼠BMSCs中的成骨分化。进行了RT-PCR,流式细胞术,细胞计数试剂盒8和膜联蛋白V-FITC / PI双重染色测定。双重敲低的miR133a和miR133b可以促进BMSC成骨分化。在最佳N / P比率(15:1)下,加载效率可以达到90%以上。CTH-antagomiR-133a / b对BMSC无细胞毒性,并减少了BMSC中miR133a和miR133b的表达。此外,基于壳聚糖的持续递送系统可以促进antagomiR-133a / b的连续给药,从而增强了体外的钙沉积和成骨特异性基因表达。在小鼠颅骨缺损模型中使用含有CTH-antagomiR-133a / b纳米粒子的持续递送系统后,新的骨形成得到增强。我们的结果表明,CTH纳米颗粒可以促进antagomiR133a / b的连续给药,从而促进成骨分化。
更新日期:2019-10-29
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