Light-Controlled BMSC Sheet-Implant Complexes with Improved Osteogenesis via an LRP5/beta-Catenin/Runx2 Regulatory Loop
Light-Controlled BMSC Sheet-Implant Complexes with Improved Osteogenesis via an LRP5/beta-Catenin/Runx2 Regulatory Loop
复制标题
光控 BMSC 片状植入物复合物通过 LRP5/β-Catenin/Runx2 调节环改善成骨作用
DOI：
10.1021/acsami.7b10184
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发表时间：
2017
影响因子：
9.5
通讯作者：
Yang GL
中科院分区：
文献类型：
--
作者：
Jiang Zhiwei;Yu Ke;Feng Yuting;Huang Tingben;Lai Kaichen;Xi Yue;Yang Guoli;Wang Huiming;Wang Ying;Yang GL
骨髓间充质干细胞（BMSC）片和钛种植体（BMSC片-种植体复合物）的组合可以加速骨整合。然而，制备BMSC片-种植体复合物的方法相当有限，BMSC片-种植体复合物的存活是关键障碍之一。在这里，我们表明，一个光控制的制造系统可以产生更少的损伤BMSC片植入复合物与改善的生存能力和成骨和非侵入性监测的BMSC片植入复合物的生存能力，使用慢病毒输送系统是可行的。增强的表达绿色荧光蛋白和荧光蛋白酶的BMSC片被用于追踪体内BMSC片-植入物复合物的活力。通过显微CT分析和硬组织切片实验评价BMSC片-种植体复合物体内成骨能力。结果表明，BMSC片-植入物复合物在植入后存活近1个月。值得注意的是，与通过机械刮擦制造的复合物相比，通过光控制造系统制造的BMSC片-植入物复合物上调了低密度脂蛋白受体相关蛋白5（LRP 5）、β-连环蛋白和runt相关转录因子2（Runx 2）的表达水平。此外，我们发现Runx 2直接与大鼠LRP 5启动子结合，LRP 5/β-catenin/Runx 2调节环有助于增强骨整合潜力。在这项研究中，我们成功地制造了BMSC片植入复合物，提高了生存能力和成骨，并建立了一个可行的，非侵入性的，和连续的方法在体内跟踪BMSC片植入复合物。我们的研究结果奠定了基础，在体内的应用BMSC片植入复合物和工程BMSC片植入复合物开辟了新的途径。
The combination of bone marrow mesenchymal stem cell (BMSC) sheets and titanium implants (BMSC sheet–implant complexes) can accelerate osseointegration. However, methods of fabricating BMSC sheet–implant complexes are quite limited, and the survival of BMSC sheet–implant complexes is one of the key barriers. Here, we show that a light-controlled fabricating system can generate less injured BMSC sheet–implant complexes with improved viability and osteogenesis and that noninvasive monitoring of the viability of BMSC sheet–implant complexes using a lentiviral delivery system is feasible. Enhanced green fluorescent protein- and luciferase-expressing BMSC sheets were used to track the viability of BMSC sheet–implant complexes in vivo. The experiments of micro-computed tomography analysis and hard tissue slices were performed to evaluate the osteogenic ability of BMSC sheet–implant complexes in vivo. The results showed that BMSC sheet–implant complexes survived for almost 1 month after implantation. Notably, BMSC sheet–implant complexes fabricated by the light-controlled fabricating system had upregulating expression levels of low-density lipoprotein-receptor-related protein 5 (LRP5), β-catenin, and runt-related transcription factor 2 (Runx2) compared to the complexes fabricated by mechanical scraping. Furthermore, we found that Runx2 directly bound to the rat LRP5 promoter and the LRP5/β-catenin/Runx2 regulatory loop contributed to the enhancement of the osseointegrating potentials. In this study, we successfully fabricated BMSC sheet–implant complexes with improved viability and osteogenesis and established a feasible, noninvasive, and continuous method for tracking BMSC sheet–implant complexes in vivo. Our findings lay the foundation for the application of BMSC sheet–implant complexes in vivo and open new avenues for engineered BMSC sheet–implant complexes.