International Journal of Medical Sciences

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17 November 2018

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Int J Med Sci 2016; 13(10):783-789. doi:10.7150/ijms.16663

Research Paper

Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats

Zi-hui Yang1,#, Bao-lei Wu1,#, Chen Ye2, Sen Jia1, Xin-jie Yang1, Rui Hou1, De-lin Lei1, ✉, Lei Wang1,2,✉

1. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
2. Shanghai Key Laboratory of Stomatology, Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, China
# Joint first authors.


Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration.

Keywords: distraction osteogenesis, mesenchymal stem cell, mandible, p38 signaling, anisomycin.

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How to cite this article:
Yang Zh, Wu Bl, Ye C, Jia S, Yang Xj, Hou R, Lei Dl, Wang L. Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats. Int J Med Sci 2016; 13(10):783-789. doi:10.7150/ijms.16663. Available from