期刊
RSC ADVANCES
卷 6, 期 41, 页码 34081-34089出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5ra24891d
关键词
-
资金
- National Natural Science Foundation of China [81320108011, 81271111, 30830108]
- Graduate Innovation Fund of Jilin University [2015050]
- Research Fund for the Doctoral Program of Higher Education of China [233200801830063, 20120061130010]
- Science Technology Program of Jilin Province [201201064]
Treating bone defects is still a challenge in clinical practice. Recently, researchers used human bone morphogenetic protein 2 gene (hBMP-2) to induce osteoblast differentiation and promote new bone formation. However, an efficient way to deliver hBMP-2 still needs to be created. In this study, we evaluated whether chitosan-polyethylenimine (CS-PEI) nanoparticle could effectively deliver hBMP-2 locally with lower or no toxicity and promote osteoblast differentiation and new bone formation in vitro and in vivo. Data demonstrated that the synthesized CS-PEI/hBMP-2 nanoparticle at a W/W ratio of 20 to 1, which was the smallest size (162 nm) and highest zeta potential (24 mV), effectively transfected MC3T3-E1 cells without cytotoxicity in vitro, and had the ability to promote cell proliferation. Interestingly, the CS-PEI/hBMP-2 nanoparticle eliminated disadvantages of lower transfection efficiency from chitosan and cytotoxicity from PEI. RT-QPCR data showed that MC3T3-E1 cells treated with CS-PEI/hBMP-2 nanoparticle dramatically expressed higher levels of BMP-2 and significantly increased gene expressions of Col1 on days 3 and 14, Sp7 on days 3, 7, and 14, and ALP on day 14. Alizarin red staining demonstrated that CS-PEI/hBMP-2 nanoparticle-treated MC3T3-E1 cells significantly increased cell mineralization. These in vitro data suggest that the CS-PEI/hBMP-2 nanoparticle can effectively induce osteogenic differentiation of MC3T3-E1 cells in vitro. Western blot analysis further demonstrated that transgene BMP-2 indeed phosphorylated Smad1/5/8, which indicates that CS-PEI/hBMP-2 nanoparticle affects cell differentiation through a BMP-2 signal pathway. Importantly, in vivo data showed that CSPEI/ hBMP-2 nanoparticle clearly promoted new bone formation at the bone defect area 12 weeks post-implantation. This indicates that synthesized CS-PEI/hBMP-2 nanoparticle has the potential to become a useful therapeutic vector for bone defect treatment with further modification.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据