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Original Article | Open Access

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

Anamaria Balic1Dilara Perver2Pierfrancesco Pagella1Hubert Rehrauer3Bernd Stadlinger4Andreas E. Moor5Viola Vogel2Thimios A. Mitsiadis1 ( )
Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland
Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zurich, Zurich, Switzerland
Functional Genomics Center Zurich, ETH Zurich and University of Zurich, Zurich, Switzerland
Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich, Switzerland
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland

These authors contributed equally: Dilara Perver, Pierfrancesco Pagella

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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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International Journal of Oral Science
Article number: 30
Cite this article:
Balic A, Perver D, Pagella P, et al. Extracellular matrix remodelling in dental pulp tissue of carious human teeth through the prism of single-cell RNA sequencing. International Journal of Oral Science, 2023, 15: 30. https://doi.org/10.1038/s41368-023-00238-z

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Received: 16 February 2023
Revised: 27 June 2023
Accepted: 06 July 2023
Published: 02 August 2023
© The Author(s) 2023

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