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2型糖尿病小鼠切牙中牙齿发育延迟及干/祖细胞分化受损

Delayed Tooth Development and the Impaired Differentiation of Stem/Progenitor Cells in Incisors from Type 2 Diabetes Mice.

作者信息

Kobayashi Yoshifumi, Huang Jia, Barnett Brandon K, Falcon Carla Y, Falcon Paul A, Hirschberg Craig S, Fine Daniel H, Ye Yi, Shimizu Emi

机构信息

Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.

Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ 07103, USA.

出版信息

Int J Mol Sci. 2024 Dec 19;25(24):13619. doi: 10.3390/ijms252413619.

Abstract

Patients with diabetes mellitus (DM) have an increased risk of tooth decay caused by alterations in their tooth development and their oral environment, as well as a tendency to present with pulp infection due to compromised immune response. The present study analyzed the characteristic alterations in tooth development under DM conditions using incisors from type 2 diabetic mouse model (T2DM mice). In micro-CT analyses, T2DM mice showed delayed dentin and enamel formation. Through transcriptomic analyses, pre-ameloblast- and pre-odontoblast-specific genes were found to be significantly decreased in the incisors of T2DM mice, whereas major ameloblast- and mature odontoblast-specific genes were not changed. Stem cell markers were decreased in T2DM mice compared to those from the control mice, suggesting that the stemness of dental pulp cells (DPCs) is attenuated in T2DM mice. In vitro analyses demonstrated that DPCs from T2DM mice have lower colony-forming units (CFU), slower propagation, and diminished differentiation characteristics compared to the control. These data suggest that T2DM conditions could impair the differentiation property of multiple progenitor/stem cells in the tooth, resulting in delayed tooth development in T2DM mice.

摘要

糖尿病(DM)患者因牙齿发育和口腔环境改变而患龋齿的风险增加,并且由于免疫反应受损而有牙髓感染的倾向。本研究使用2型糖尿病小鼠模型(T2DM小鼠)的门牙分析了糖尿病条件下牙齿发育的特征性改变。在显微CT分析中,T2DM小鼠的牙本质和釉质形成延迟。通过转录组分析,发现前成釉细胞和前成牙本质细胞特异性基因在T2DM小鼠的门牙中显著减少,而主要的成釉细胞和成熟成牙本质细胞特异性基因没有变化。与对照小鼠相比,T2DM小鼠的干细胞标志物减少,这表明T2DM小鼠牙髓细胞(DPCs)的干性减弱。体外分析表明,与对照相比,T2DM小鼠的DPCs具有更低的集落形成单位(CFU)、更慢的增殖速度和减弱的分化特性。这些数据表明,T2DM条件可能损害牙齿中多个祖细胞/干细胞的分化特性,导致T2DM小鼠牙齿发育延迟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52dc/11728242/7c9446857171/ijms-25-13619-g0A1.jpg

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