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使用猪模型研究牙齿缺失对面部骨骼生长的影响。

Investigating the Influence of a Tooth Absence on Facial Bone Growth Using a Porcine Model.

作者信息

Szkopek Dominika, Wychowański Piotr, Zaworski Kamil, Seklecka Blanka, Starzyński Rafał, Lipiński Paweł, Pierzynowska Kateryna, Pierzynowski Stefan G, Donaldson Janine, Paczewski Łukasz, Woliński Jarosław

机构信息

Laboratory of Large Animal Models, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.

Oral Surgery and Implantology Unit, Division of Oral Surgery and Implantology, Department of Head and Neck, Institute of Clinical Dentistry, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universita Cattolica del Sacro Coure, 00168 Rome, Italy.

出版信息

Int J Mol Sci. 2024 Nov 21;25(23):12509. doi: 10.3390/ijms252312509.

Abstract

With the current state of knowledge regarding disorders of facial bone development, including anodontia, the development of a suitable animal model for preclinical studies is essential. The agenesis of dental buds occurs in about 25% of the human population. Prospects for treatment include the use of growth factors, stem cells, and bioengineering. This study aimed to investigate the influence of a tooth absence on facial bone growth, develop a technique for the application of growth factors to the developing bone, and analyze the comparative effect of the application of selected active proteins on the growth of the maxilla and mandible. Piglets underwent germectomy, followed by computed tomography and X-ray; morphometric and histological analyses of the bones were performed, blood bone morphogenetic protein 2 and platelet-derived growth factor concentrations were determined, and the transcriptomic profile of the dentate ligament was analyzed using DNA microarrays. It was not possible to identify the most effective growth factor application algorithm for achieving normal jaw development. Normal mandibular bone structure and oral mucosa structure were observed in the germectomy groups with growth factor augmentation. The average height of the mandibular alveolar part in the area of the removed dental buds was significantly lower compared with that of the inoperable side, 3 months after surgery. However, no significant differences were found in the serum concentrations of BMP-2 and PDGF between groups. The animal model of bone development disorders (including anodontia) developed in the current study and the scheme for evaluating the efficacy and safety of the application of replacement therapy for craniofacial malformations are important in the development of the discipline and represent an important contribution to the introduction of treatment methods.

摘要

鉴于目前对面部骨骼发育障碍(包括无牙症)的了解情况,开发一种适用于临床前研究的动物模型至关重要。牙胚发育不全在约25%的人群中出现。治疗前景包括使用生长因子、干细胞和生物工程技术。本研究旨在调查牙齿缺失对面部骨骼生长的影响,开发一种将生长因子应用于发育中骨骼的技术,并分析所选活性蛋白应用于上颌骨和下颌骨生长的比较效果。对仔猪进行了牙胚切除手术,随后进行计算机断层扫描和X射线检查;对骨骼进行了形态计量学和组织学分析,测定了血液中骨形态发生蛋白2和血小板衍生生长因子的浓度,并使用DNA微阵列分析了齿状韧带的转录组谱。无法确定实现正常颌骨发育的最有效生长因子应用算法。在生长因子增强的牙胚切除组中观察到正常的下颌骨结构和口腔黏膜结构。术后3个月,切除牙胚区域的下颌牙槽部分平均高度明显低于未手术侧。然而,各实验组间骨形态发生蛋白-2(BMP-2)和血小板衍生生长因子(PDGF)的血清浓度没有显著差异。本研究建立的骨骼发育障碍(包括无牙症)动物模型以及评估颅面畸形替代疗法有效性和安全性的方案对该学科的发展具有重要意义,是对引入治疗方法的重要贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc3/11640821/6e3751bbf8be/ijms-25-12509-g001.jpg

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