title: Targeting P38 Pathway Regulates Bony FormationviaMSC Recruitment during Mandibular Distraction Osteogenesis in Rats.
abstract: 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.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Chen
authors.initials: C
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.
authors.forename: De-Lin
authors.initials: DL
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, China.; 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008334:Mandible / Q000502:physiology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction / Q000379:methods*; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D000841:Anisomycin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: anisomycin.; distraction osteogenesis; mandible; mesenchymal stem cell; p38 signaling