Feng Guijuan, Zhang Jinlong, Feng Xingmei, Wu Senbin, Huang Dan, Hu Jing, Zhu Songsong, Song Donghui
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Differentiation. 2016 Oct-Nov;92(4):195-203. doi: 10.1016/j.diff.2016.06.001. Epub 2016 Jun 14.
Distraction osteogenesis (DO) remains a major challenge in orthopedic and craniofacial surgery. The transplantion of mesenchymal stem cells (MSCs) could reduce the treatment period and the associated complications by increasing new bone formation during long-bone DO. Runt-related transcription factor 2 (Runx2) encodes a nuclear protein that is a pivotal regulator of osteoblast differentiation. It significantly stimulates calcium accumulation and alkaline phosphatase (ALP) activity in dental pulp stem cells (DPSCs). In this study, we investigated the effects of gene therapy using Runx2 on new bone formation during tibia DO of rabbits. The distraction gap of the rabbits was injected with adenovirus (Adv)-Runx2-green fluorescent protein (GFP)-transfected DPSCs (overexpression group, Group OE) or Adv-GFP-transfected DPSCs (negative control group, Group NC). Rabbits in the control group (Groups CON) were injected with physiologic saline. The generation of new bone tissue in the distraction gap was studied by radiographic examination, micro-computed tomography (CT) evaluation, histological analyze, and Mechanical testing at weeks 8 in the consolidation period. Excellent bone formation in the distracted callus was observed in Group OE and Group NC. Moreover, the OE group showed better bone formation and the highest bone mineral density (BMD) and bone mineral content (BMC). Group CON animals showed inadequate bone formation in the distracted callus compared to the other groups. The results suggest that gene therapy using Runx2-modified DPSCs was more effective during bone deposition and new bone formation in tibia DO.
牵张成骨术（DO）在骨科和颅面外科手术中仍然是一项重大挑战。间充质干细胞（MSCs）的移植可以通过增加长骨牵张成骨过程中的新骨形成来缩短治疗周期并减少相关并发症。 runt相关转录因子2（Runx2）编码一种核蛋白，它是成骨细胞分化的关键调节因子。它能显著刺激牙髓干细胞（DPSCs）中的钙积累和碱性磷酸酶（ALP）活性。在本研究中，我们研究了使用Runx2进行基因治疗对兔胫骨牵张成骨过程中新骨形成的影响。将腺病毒（Adv）-Runx2-绿色荧光蛋白（GFP）转染的DPSCs（过表达组，OE组）或Adv-GFP转染的DPSCs（阴性对照组，NC组）注入兔的牵张间隙。对照组（CON组）的兔注射生理盐水。在愈合期第8周，通过放射学检查、微计算机断层扫描（CT）评估、组织学分析和力学测试研究牵张间隙中新骨组织的生成。在OE组和NC组中观察到牵张骨痂中有良好的骨形成。此外，OE组显示出更好的骨形成以及最高的骨密度（BMD）和骨矿物质含量（BMC）。与其他组相比，CON组动物在牵张骨痂中的骨形成不足。结果表明，使用Runx2修饰的DPSCs进行基因治疗在兔胫骨牵张成骨的骨沉积和新骨形成过程中更有效。
