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Local delivery of small interfering RNA using biodegradable polymer application to enhance bone morphogenetic protein-induced bone formation

使用可生物降解聚合物局部递送小干扰RNA以增强骨形态发生蛋白诱导的骨形成

基本信息

批准号：
21791408
负责人：
SUZUKI Akinobu
金额：
$ 2.75万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791408/
关键词：
ポリマー骨形成蛋白(Bone morphogenetic protein;BMP)Noggin 骨再生 siRNA rhBMP-2

项目摘要

In this study, we investigated the efficacy of a biodegradable hydrogel, poly-D,L-lactic acid-p-dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier. PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was confirmed by fluorescent microscopy. The fluorescence intensity was dose dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate its biological efficiency, noggin (antagonoist to BMPs) gene silencing with siRNA (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin expression and the level of performance of BMP, indicated by ectopic bone formation. Noggin gene expression induced by BMP-2 was suppressed by addition of siRNA /Noggin to the implant, and the ectopic-bone formation induced by implants with both BMP-2 and siRNA/Noggin was significantly greater than those induced by implants with BMP-2 alone. These results indicate the efficacy of local delivery of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP and promoted new bone formation by suppressing gene expression of Noggin.

在这项研究中，我们研究了可生物降解的水凝胶，聚-D，L-乳酸-对二氧杂环己酮-聚乙二醇嵌段共聚物（PLA-DX-PEG），作为siRNA载体的功效。将具有或不具有荧光素标记的dsRNA的PLA-DX-PEG颗粒植入小鼠背侧肌袋中。通过荧光显微镜证实了聚合物周围dsRNA的细胞摄取。荧光强度是dsRNA的剂量依赖性的，并且表现出时间依赖性降低。为了研究其生物学效率，通过BMP-2诱导的头蛋白表达的抑制量和由异位骨形成指示的BMP的性能水平来检查用siRNA（siRNA/Noggin）进行的头蛋白（对BMP的抑制）基因沉默。通过向植入物中添加siRNA /Noggin抑制由BMP-2诱导的Noggin基因表达，并且由具有BMP-2和siRNA/Noggin的植入物诱导的异位骨形成显著大于由仅具有BMP-2的植入物诱导的异位骨形成。这些结果表明PLA-DX-PEG聚合物局部递送siRNA的功效，其通过抑制Noggin的基因表达来增强BMP的骨诱导作用并促进新骨形成。