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Home / Equine Research Bank / PLoS One / microRNAs are differentially expressed in equine plasma of h...
PloS one2024; 19(2); e0297303; doi: 10.1371/journal.pone.0297303

microRNAs are differentially expressed in equine plasma of horses with osteoarthritis and osteochondritis dissecans versus control horses.

Abstract: Osteoarthritis (OA) is a leading cause of lameness in horses with no effective disease-modifying treatment and challenging early diagnosis. OA is considered a disease of the joint involving the articular cartilage, subchondral bone, synovial membrane, and ligaments. Osteochondritis dissecans (OCD) is a joint disease consisting of focal defects in the osteochondral unit which may progress to OA later in life. MicroRNAs (miRNAs) have been recognized as small non-coding RNAs that regulate a variety of biological processes and have been detected in biological fluids. MiRNAs are currently investigated for their utility as biomarkers and druggable targets for a variety of diseases. The current study hypothesizes that miRNA profiles can be used to actively monitor joint health and differences in miRNA profiles will be found in healthy vs diseased joints and that differences will be detectable in blood plasma of tested horses. Five horses with OA, OCD, and 4 controls (C) had blood plasma and synovial fluid collected. Total RNA, including miRNA was isolated before generating miRNA libraries from the plasma of the horses. Libraries were sequenced at the Schroeder Arthritis Institute (Toronto). Differential expression analysis was done using DESeq2 and validated using ddPCR. KEGG pathway analysis was done using mirPath v.3 (Diana Tools). 57 differentially expressed miRNAs were identified in OA vs C plasma, 45 differentially expressed miRNAs in OC vs C plasma, and 21 differentially expressed miRNAs in OA vs OCD plasma. Notably, miR-140-5p expression was observed to be elevated in OA synovial fluid suggesting that miR-140-5p may serve as a protective marker early on to attenuate OA progression. KEGG pathway analysis of differentially expressed plasma miRNAs showed relationships with glycan degradation, glycosaminoglycan degradation, and hippo signaling pathway. Interestingly, ddPCR was unable to validate the NGS data suggesting that isomiRs may play an integral role in miRNA expression when assessed using NGS technologies.
Copyright: © 2024 Antunes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Publication Date: 2024-02-23 PubMed ID: 38394252PubMed Central: PMC10890772DOI: 10.1371/journal.pone.0297303Google 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.

This research explores the presence and variance in microRNAs in the blood plasma and synovial fluid of horses suffering from osteoarthritis and osteochondritis dissecans compared to healthy ones. The research attempts to use this as a marker for detecting and monitoring these joint health issues.

Introduction and Hypothesis

  • The study is situated in the context of osteoarthritis and osteochondritis dissecans (OCD), two common joint diseases in horses which lack effective treatments and present difficulties in early diagnosis.
  • The researchers hypothesize that profiling of microRNAs (miRNAs) – small non-coding RNAs found in biological fluids – could be used to monitor the state of joint health in the animals.
  • They expect to find differences in miRNA profiles between healthy and diseased joints, and believe that such differences would be detectable in the blood plasma of the horses under study.

Methods

  • They collected blood plasma and synovial fluid from five horses diagnosed with osteoarthritis or OCD, and four healthy control horses.
  • Total RNA, inclusive of miRNA, was isolated from the plasma of these horses to create miRNA libraries.
  • These libraries were then sequenced at the Schroeder Arthritis Institute and differentially expressed miRNAs were identified using a data analysis technique known as DESeq2.
  • The sequencing data was validated by droplet digital PCR (ddPCR) and a pathway analysis was conducted using mirPath v.3.

Results

  • Differential expression analysis revealed 57, 45, and 21 differently expressed miRNAs in the plasma of OA vs control, OCD vs control, and OA vs OCD horses, respectively.
  • The microRNA miR-140-5p was found to be over expressed in osteoarthritic synovial fluid, suggesting its potential as a protective marker that could attenuate OA progression.
  • Pathway analysis showed correlations between the differently expressed plasma miRNAs and pathways involved in glycan degradation, glycosaminoglycan degradation, and the Hippo signaling pathway.
  • The researchers noted that ddPCR could not validate the next-generation sequencing (NGS) data, highlighting the critical role of isomiRs (miRNA variants) in miRNA expression determined by NGS.

Cite This Article

APA
Antunes J, Salcedo-Jiménez R, Lively S, Potla P, Coté N, Dubois MS, Koenig J, Kapoor M, LaMarre J, Koch TG. (2024). microRNAs are differentially expressed in equine plasma of horses with osteoarthritis and osteochondritis dissecans versus control horses. PLoS One, 19(2), e0297303. https://doi.org/10.1371/journal.pone.0297303

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 19
Issue: 2
Pages: e0297303
PII: e0297303

Researcher Affiliations

Antunes, Joshua
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Salcedo-Jiménez, Ramés
  • Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Lively, Starlee
  • Osteoarthritis Research Program, Division of Orthopedics, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Potla, Pratibha
  • Osteoarthritis Research Program, Division of Orthopedics, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Coté, Nathalie
  • Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Dubois, Marie-Soleil
  • Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Koenig, Judith
  • Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Kapoor, Mohit
  • Osteoarthritis Research Program, Division of Orthopedics, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
LaMarre, Jonathan
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Koch, Thomas Gadegaard
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.

MeSH Terms

  • Animals
  • Horses / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Osteochondritis Dissecans / genetics
  • Osteochondritis Dissecans / veterinary
  • Osteoarthritis / genetics
  • Osteoarthritis / veterinary
  • Osteoarthritis / diagnosis
  • Joint Diseases
  • Synovial Membrane / metabolism

Conflict of Interest Statement

I have read the journal’s policy and the authors of the manuscript have the following competing interests: Mohit Kapoor has a patent on microRNA biomarkers for cartilage degeneration (Patent Number: 10888577). There are no other competing interests.

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