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Home / Equine Research Bank / Ann Transl Med / Characterization of the single cell landscape in normal and ...
Annals of translational medicine2024; 12(5); 88; doi: 10.21037/atm-24-40

Characterization of the single cell landscape in normal and osteoarthritic equine joints.

Abstract: Osteoarthritis (OA) is a major source of pain and disability worldwide. Understanding of disease progression is evolving, but OA is increasingly thought to be a multifactorial disease in which the innate immune system plays a role in regulating and perpetuating low-grade inflammation. The aim of this study was to enhance our understanding of OA immunopathogenesis through characterization of the transcriptomic responses in OA joints, with the goal to facilitate the development of targeted therapies. Unassigned: Single-cell RNA sequencing (scRNA-seq) was completed on cells isolated from the synovial fluid of three normal and three OA equine joints. In addition to synovial fluid, scRNA-seq was also performed on synovium from one normal joint and one OA joint. Unassigned: Characterization of 28,639 cells isolated from normal and OA-affected equine synovial fluid revealed the composition to be entirely immune cells (CD45+) with 8 major populations and 26 subpopulations identified. In synovial fluid, we found myeloid cells (macrophage and dendritic cells) to be overrepresented and T cells (CD4 and CD8) to be underrepresented in OA relative to normal joints. Through subcluster and differential abundance analysis of T cells we further identified a relative overrepresentation of IL23R+ gamma-delta (γδ) T cells in OA-affected joints (a cell type we report to be enriched in gene signatures associated with T helper 17 mediated immunity). Analysis of an additional 17,690 cells (11 distinct cell type clusters) obtained from synovium of one horse led to the identification of an OA-associated reduction in the relative abundance of synovial macrophages, which contrasts with the increased relative abundance of macrophages in synovial fluid. Completion of cell-cell interaction analysis implicated myeloid cells in disease progression, suggesting that the myeloid-myeloid interactions were increased in OA-affected joints. Unassigned: Overall, this work provides key insights into the composition of equine synovial fluid and synovium in health and OA. The data generated in this study provides equine-specific cell type gene signatures which can be applied to future investigations. Furthermore, our analysis highlights the potential role of macrophages and IL23R+ γδ T cells in OA immunopathogenesis.
2024 AME Publishing Company. All rights reserved.
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Publication Date: 2024-10-15 PubMed ID: 39507442PubMed Central: PMC11534742DOI: 10.21037/atm-24-40Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on understanding Osteoarthritis (OA) progression by studying the transcriptomic responses in OA-affected equine horse joints. Changes in the composition of immune cells present in the joint’s synovial fluid between healthy and OA-affected horses were observed.

Research Methodology

  • The research conducted single-cell RNA sequencing (scRNA-seq) on cells taken from synovial fluid in three normal and three OA-affected horse joints. This effective technique allows for gene expression analysis at a single-cell resolution.
  • Cells from one normal and one OA-affected synovium (joint lining) were also sequenced through scRNA-seq.
  • The isolated cells were then categorized based on the findings of the scRNA-seq analysis.

Main Findings

  • The researchers identified 28,639 cells from the synovial fluid of normal and OA-affected horse joints, all of which were immune cells.
  • Eight major cell populations and 26 subpopulations were found. Among these, they noticed a significant deviation in the representation of myeloid cells (macrophages and dendritic cells) and T cells (CD4 and CD8) in OA-affected joints compared to healthy ones. Particularly, myeloid cells were overrepresented and T cells were underrepresented in OA joints.
  • The study also highlighted an overrepresentation of IL23R gamma-delta (γδ) T cells in OA-affected joints. These cells are typically associated with T helper 17 mediated immunity.
  • An analysis of 17,690 cells taken from the synovium of one horse showed a decrease in the relative abundance of synovial macrophages in OA-affected joints. This finding contrasted with the increase in macrophage levels observed in synovial fluid from OA-affected joints.
  • The research concluded that myeloid cells play a crucial role in disease progression as increased myeloid-myeloid interactions were observed in OA-affected joints.

Implications

  • This research offers valuable insight into the changes that occur in the cellular composition of equine synovial fluid and synovium during OA disease progression.
  • It highlights the importance of immune cells like macrophages and T-cells in the pathogenesis of OA.
  • The findings could help develop targeted therapies for OA by understanding the roles of different cell types in the disease.
  • The discovery of an equine-specific cell type gene signature provides a useful tool for future research into equine joint diseases.

Cite This Article

APA
Ammons DT, Chow L, Goodrich L, Bass L, Larson B, Williams ZJ, Stoneback JW, Dow S, Pezzanite LM. (2024). Characterization of the single cell landscape in normal and osteoarthritic equine joints. Ann Transl Med, 12(5), 88. https://doi.org/10.21037/atm-24-40

Publication

Annals of translational medicine
ISSN: 2305-5839
NlmUniqueID: 101617978
Country: China
Language: English
Volume: 12
Issue: 5
Pages: 88

Researcher Affiliations

Ammons, Dylan T
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Chow, Lyndah
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Goodrich, Laurie
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Bass, Luke
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Larson, Blaine
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Williams, Zoë J
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Stoneback, Jason W
  • Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Dow, Steven
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
  • Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Pezzanite, Lynn M
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
  • Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Grant Funding

  • T32 OD010437 / NIH HHS
  • T32 TR004366 / NCATS NIH HHS
  • TL1 TR002533 / NCATS NIH HHS

Conflict of Interest Statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-24-40/coif). Z.J.W. reports that stipend funding was provided by NIH/NCATS Colorado CTSA T32TR004366. L.M.P. reports that this study was funded by the Foundation for the Horse, Grayson Jockey Club Research Foundation, Colorado State University College Research Council Interdisciplinary Pilot Award, NIH/NCATS CTSA 5TL1TR002533-02 (L.M.P.), NIH 5T32OD010437-19 (L.M.P.), and Carolyn Quan and Porter Bennett. The other authors have no conflicts of interest to declare.

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