Calcitonin gene‑related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats

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

doi:10.3892/etm.2019.7659

Calcitonin gene‑related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats

Authors:
- Sen Jia
- Shi‑Jian Zhang
- Xu‑Dong Wang
- Zi‑Hui Yang
- Ya‑Nan Sun
- Anand Gupta
- Rui Hou
- De‑Lin Lei
- Kai‑Jin Hu
- Wei‑Min Ye
- Lei Wang
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Affiliations: Department of Oral and Maxillofacial Surgery, School of Stomatology Xi'an Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Oral and Maxillofacial‑Head and Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, 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, State Key Laboratory of Military Stomatology, Department of Pediatric Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Oral and Maxillofacial Surgery, Government Medical College and Hospital, Chandigarh, Haryana 160030, India
Published online on: June 11, 2019 https://doi.org/10.3892/etm.2019.7659
Pages: 1039-1046
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study evaluated the effects of calcitonin gene‑related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) in vitro 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 in vivo 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 in vitro 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 in vivo 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.

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