Extracellular matrix remodelling in dental pulp tissue of carious human teeth through the prism of single-cell RNA sequencing.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Anamaria Balic, Dilara Perver, Pierfrancesco Pagella, Hubert Rehrauer, Bernd Stadlinger, Andreas E Moor, Viola Vogel, Thimios A Mitsiadis
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Abstract

Carious lesions are bacteria-caused destructions of the mineralised dental tissues, marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue. While major molecular players in tooth decay have been uncovered during the past years, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. In this study we used single-cell RNA sequencing analysis, supplemented with immunostaining, to generate a comprehensive single-cell atlas of the pulp of carious human teeth. Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth, such as immune cells, mesenchymal stem cells (MSC) and fibroblasts, when compared to the pulp of healthy human teeth. Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters. These changes include the upregulation of genes encoding extracellular matrix (ECM) components, including COL1A1 and Fibronectin (FN1), and the enrichment of the fibroblast cluster with myofibroblasts. The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses. Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues, compared to the healthy ones. The present data demonstrate molecular, cellular and biomechanical alterations in the pulp of human carious teeth, indicative of extensive ECM remodelling, reminiscent of fibrosis observed in other organs. This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.

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单细胞RNA测序技术在龋齿牙髓组织细胞外基质重构中的应用。
龋齿病变是细菌引起的矿化牙组织的破坏,其特征是同时激活免疫反应和软牙髓组织内的再生事件。虽然在过去的几年中发现了蛀牙的主要分子作用,但患病牙髓的分子和细胞景观的详细地图仍然缺失。在这项研究中,我们使用单细胞RNA测序分析,辅以免疫染色,生成了一个全面的单细胞牙髓图谱。我们的数据表明,与健康的人牙髓相比,龋齿牙髓内的各种细胞团(如免疫细胞、间充质干细胞(MSC)和成纤维细胞)发生了变化。龋齿牙髓组织中的主动免疫反应伴随着成纤维细胞和间充质干细胞簇的特异性变化。这些变化包括编码细胞外基质(ECM)成分的基因上调,包括COL1A1和纤维连接蛋白(FN1),以及肌成纤维细胞簇的富集。免疫染色分析进一步证实了龋牙髓组织ECM组成的增量变化。在机械应变条件下对纤维连接蛋白纤维的评估显示,与健康牙髓组织相比,龋齿牙髓组织的张力显著降低。目前的数据表明,人类龋齿牙髓中的分子、细胞和生物力学改变,表明广泛的ECM重塑,使人想起在其他器官中观察到的纤维化。这个全面的人类龋齿图谱可以促进未来牙齿病理学的研究,并使跨患病器官的比较分析成为可能。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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