Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

  1. Yi Fan
  2. Ping Lyu
  3. Ruiye Bi
  4. Chen Cui
  5. Ruoshi Xu
  6. Clifford J Rosen
  7. Quan Yuan  Is a corresponding author
  8. Chenchen Zhou  Is a corresponding author
  1. Sichuan University, China
  2. Sun Yat-sen University, China
  3. Maine Medical Center Research Institute, United States

Abstract

Oral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher levels of osteogenic related markers, including Sparc and Col1a1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the protective process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7, Figure1-figure supplement 1 and Figure5-figure supplement 3.

The following data sets were generated

Article and author information

Author details

  1. Yi Fan

    Department of Cariology and Endodontics, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7511-9872
  2. Ping Lyu

    Department of Cariology and Endodontics, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9908-9989
  3. Ruiye Bi

    Department of Orthognathic and TMJ Surgery, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Chen Cui

    Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Ruoshi Xu

    Department of Cariology and Endodontics, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Clifford J Rosen

    Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3436-8199
  7. Quan Yuan

    Department of Oral Implantology, Sichuan University, Chengdu, China
    For correspondence
    yuanquan@scu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  8. Chenchen Zhou

    Department of Orthodontics, Sichuan University, Chengdu, China
    For correspondence
    chenchenzhou5510@scu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6427-5869

Funding

National Natural Science Foundation of China (81800928)

  • Yi Fan

National Natural Science Foundation of China (81901040)

  • Chenchen Zhou

National Natural Science Foundation of China (82171001)

  • Chenchen Zhou

Young Elite Scientist Sponsorship Program by CAST (2020QNRC001)

  • Chenchen Zhou

Young Elite Scientist Sponsorship Program by CAST (2018QNR001)

  • Yi Fan

Sichuan Science and Technology Program (2019YJ0054)

  • Yi Fan

Research Funding from West China School/Hospital of Stomatology Sichuan University (RCDWJS2021-1)

  • Yi Fan

State Key Laboratory of Oral Diseases Open Funding Grant (SKLOD-R013)

  • Yi Fan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Di Chen, Chinese Academy of Sciences, China

Ethics

Animal experimentation: All animal experiments were carried out in accordance with the guidelines of the Institutional Animal Care and Use Committee at the State Key Laboratory of Oral Diseases, Sichuan University (Permit Number: WCHSIRB-D-2021-339).

Human subjects: This study was permitted by the Ethical Committees of the West China Hospital of Stomatology, Sichuan University (Permit Number: WCHSIRB-D-2021-292). Written informed consent was obtained from all patients.

Version history

  1. Received: August 8, 2022
  2. Preprint posted: September 14, 2022 (view preprint)
  3. Accepted: January 30, 2023
  4. Accepted Manuscript published: February 1, 2023 (version 1)
  5. Version of Record published: February 13, 2023 (version 2)

Copyright

© 2023, Fan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yi Fan
  2. Ping Lyu
  3. Ruiye Bi
  4. Chen Cui
  5. Ruoshi Xu
  6. Clifford J Rosen
  7. Quan Yuan
  8. Chenchen Zhou
(2023)
Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling
eLife 12:e82537.
https://doi.org/10.7554/eLife.82537

Share this article

https://doi.org/10.7554/eLife.82537

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