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炎症和对细菌感染的反应作为马牙骨质吸收和牙骨质增生的潜在驱动因素:蛋白质组学见解

Inflammation and response to bacterial infection as potential drivers of equine odontoclastic tooth resorption and hypercementosis: A proteomics insight.

作者信息

Jensen Anders, Clarke Emily J, Nugent Zoe, Paice Emily, Gringel Iris, Yamamoto Kazuhiro, Rocchigiani Guido, Peffers Andrew J, Cooper Lee, Peffers Mandy J

机构信息

University of Liverpool, Institute of Life Course and Medical Sciences, William Henry Duncan Building, Liverpool, UK.

University of Liverpool, Institute of Infection, Veterinary and Ecological Sciences, Leahurst Campus, Neston, UK.

出版信息

Equine Vet J. 2025 Jul;57(4):977-990. doi: 10.1111/evj.14469. Epub 2025 Jan 8.

Abstract

BACKGROUND

Equine dental diseases significantly impact a horse's overall health, performance and quality of life. They can result in secondary infections and digestive disturbances, potentially leading to colic. A recently described disease affecting the incisors of horses is equine odontoclastic tooth resorption and hypercementosis (EOTRH). Understanding EOTRH is crucial for early diagnosis, effective management and prevention of its severe consequences.

OBJECTIVES

To determine proteomic differences in incisor cementum in horses with and without clinical EOTRH.

STUDY DESIGN

Comparative and observational clinical study.

METHODS

Teeth were extracted (N = 5) and cementum was isolated using a diamond wire. Proteins were extracted using an optimised sequential workflow, and trypsin was digested for mass spectrometry. Protein identification and label-free quantification were undertaken.

RESULTS

In total 1149 unique proteins were detected in cementum across all samples. We identified four proteins exclusively in EOTRH-affected cementum. EOTRH samples showed a higher heterogeneity than healthy samples. In total, 54 proteins were increased in EOTRH, and 64 proteins were reduced (adjusted p-value <0.05). Inflammatory proteins, such as cathepsin G (p = 0.004), neutrophil elastase (p = 0.003), bactericidal permeability-increasing protein (p = 0.002), azurocidin (p = 0.003) and lactotransferrin (p = 0.002) were all increased in EOTRH. Pathway analysis revealed that antimicrobial peptides (Z score 2.65, p = 1.93E-09) and neutrophil degranulation (Z-score 1.89, p = 1.7E-04) were commonly up-regulated canonical pathways.

MAIN LIMITATIONS

The sample size was limited. Lack of age-matched healthy controls.

CONCLUSION

EOTRH leads to biochemical changes within the cementum proteome, which are important in explaining the physiological changes occurring in disease. Differentially abundant proteins may represent promising biomarkers for earlier disease detection and the establishment of a cell-based model could provide further insight into the role these proteins play in hypercementosis and resorption.

摘要

背景

马牙病会严重影响马的整体健康、性能和生活质量。它们可导致继发感染和消化紊乱,有可能引发绞痛。一种最近描述的影响马切牙的疾病是马破牙细胞性牙骨质吸收和牙骨质增生(EOTRH)。了解EOTRH对于早期诊断、有效管理和预防其严重后果至关重要。

目的

确定患有和未患有临床EOTRH的马切牙牙骨质中的蛋白质组差异。

研究设计

比较性和观察性临床研究。

方法

拔牙(N = 5),使用金刚石线分离牙骨质。使用优化的连续工作流程提取蛋白质,并用胰蛋白酶消化以进行质谱分析。进行蛋白质鉴定和无标记定量。

结果

在所有样本的牙骨质中总共检测到1149种独特蛋白质。我们在受EOTRH影响的牙骨质中仅鉴定出四种蛋白质。EOTRH样本显示出比健康样本更高的异质性。总体而言,EOTRH中有54种蛋白质增加,64种蛋白质减少(校正p值<0.05)。炎症蛋白,如组织蛋白酶G(p = 0.004)、中性粒细胞弹性蛋白酶(p = 0.003)、杀菌通透性增加蛋白(p = 0.002)、天青杀素(p = 0.003)和乳铁传递蛋白(p = 0.002)在EOTRH中均增加。通路分析显示抗菌肽(Z评分2.65,p = 1.93E-09)和中性粒细胞脱颗粒(Z评分1.89,p = 1.7E-04)是常见的上调经典通路。

主要局限性

样本量有限。缺乏年龄匹配的健康对照。

结论

EOTRH导致牙骨质蛋白质组内的生化变化,这对于解释疾病中发生的生理变化很重要。差异丰富的蛋白质可能是早期疾病检测中有前景的生物标志物, 建立基于细胞的模型可以进一步深入了解这些蛋白质在牙骨质增生和吸收中所起的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efb5/12135756/3f6d7c7bdb92/EVJ-57-977-g001.jpg

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