Jia Sen, Zhang Shi-Jian, Wang Xu-Dong, Yang Zi-Hui, Sun Ya-Nan, Gupta Anand, Hou Rui, Lei De-Lin, Hu Kai-Jin, Ye Wei-Min, Wang Lei
Department of Oral and Maxillofacial Surgery, School of Stomatology Xi'an Medical University, Xi'an, Shaanxi 710032, P.R. China.
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1039-1046. doi: 10.3892/etm.2019.7659. Epub 2019 Jun 11.
The present study evaluated the effects of calcitonin gene-related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) and in a rat model of mandibular distraction osteogenesis (MDO). Rat BMMSCs were isolated then treated with CGRP or CGRP antagonist (CGRP8-37). The proliferation and migration ability of BMMSCs was determined using 5-bromo-2'-deoxyuridine and Transwell assays, respectively. Osteogenic-related gene expression was analyzed with reverse transcription-quantitative polymerase chain reaction. For the analysis, thirty MDO rats were randomly assigned to control, CGRP or CGRP8-37 groups. To evaluate the mobilization of BMMSCs, nestin and stromal cell-derived factor 1 (SDF-1) were detected by immunohistochemistry and ELISA. Rats were sacrificed following 14 days and new bone formation was assessed by histological and micro-computed tomography analysis. In the results, the CGRP group demonstrated significantly higher migration and proliferation, as well as enhanced alkaline phosphatase and runt-related transcription factor 2 expression compared with the control. In the experiments, bone mineral density of the newly formed bone in the CGRP group was significantly higher than controls. The nestin and SDF-1 expression in the CGRP group was also significantly upregulated. In conclusion, the present study demonstrated that CGRP administration increased new bone formation, possibly via enhancing BMMSC migration and differentiation in MDO rats.
本研究评估了降钙素基因相关肽（CGRP）对骨髓间充质干细胞（BMMSCs）的影响，并在大鼠下颌骨牵张成骨（MDO）模型中进行了研究。分离大鼠BMMSCs，然后用CGRP或CGRP拮抗剂（CGRP8-37）处理。分别使用5-溴-2'-脱氧尿苷和Transwell试验测定BMMSCs的增殖和迁移能力。用逆转录定量聚合酶链反应分析成骨相关基因的表达。为了进行分析，将30只MDO大鼠随机分为对照组、CGRP组或CGRP8-37组。为了评估BMMSCs的动员情况，通过免疫组织化学和酶联免疫吸附测定法检测巢蛋白和基质细胞衍生因子1（SDF-1）。14天后处死大鼠，通过组织学和显微计算机断层扫描分析评估新骨形成情况。结果显示，与对照组相比，CGRP组的迁移和增殖明显更高，碱性磷酸酶和 runt相关转录因子2的表达也增强。在实验中，CGRP组新形成骨的骨密度明显高于对照组。CGRP组中巢蛋白和SDF-1的表达也明显上调。总之，本研究表明，给予CGRP可增加新骨形成，可能是通过增强MDO大鼠中BMMSC的迁移和分化来实现的。
