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Home / Equine Research Bank / Int J Mol Sci / Synovial Fluid and Serum MicroRNA Signatures in Equine Osteo...
International journal of molecular sciences2025; 26(22); 11190; doi: 10.3390/ijms262211190

Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis.

Abstract: The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n = 4) and OA (n = 9) horses and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) was selected for validation in an independent cohort (serum, n = 46; SF, n = 88). The effect of clinical variables on miRNA expression was also assessed. Sequencing analyses found 43 and 23 differentially expressed miRNAs in serum and SF samples, respectively. Pathway analysis showed miRNAs were involved in inflammatory disease/response and associated with OA pathways. miRNA expression in serum was strongly associated with the horses' workload, while age had a pronounced influence on miRNA expression in SF. Distinct patterns of miRNA differential expression were observed in serum and SF samples from horses with OA compared to controls. miR-199a-3p and miR-148a warrant further investigation as potential biomarkers of equine OA. Further characterization of these molecular changes could provide novel insights into the mechanisms of early OA.
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Publication Date: 2025-11-19 PubMed ID: 41303673PubMed Central: PMC12652959DOI: 10.3390/ijms262211190Google 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.

Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis

Objective Overview

  • This study aimed to identify specific microRNAs (miRNAs) in blood serum and synovial fluid that differ between healthy horses and those with osteoarthritis (OA), to find potential biomarkers for diagnosing the disease.

Background

  • Osteoarthritis (OA) is a common degenerative joint disease in horses leading to pain and reduced mobility.
  • MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and can serve as biomarkers for various diseases.
  • Serum and synovial fluid (the lubricating fluid in joints) are accessible fluids where miRNA expression can reflect disease states.

Methods

  • Samples were collected from two groups of horses: controls (n=4) and those with OA (n=9).
  • Total RNA was extracted from serum and synovial fluid samples and sequenced to profile miRNA expression patterns.
  • Differential expression analysis identified miRNAs with significant changes between OA and control samples.
  • Pathway analysis was conducted to determine biological processes and disease pathways linked to the identified miRNAs.
  • miRNA target prediction tools helped identify potential genes regulated by these miRNAs.
  • A subset of six miRNAs showing notable differences (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p, and eca-miR-23b) were selected for further validation.
  • Validation was performed with a larger independent cohort: serum samples from 46 horses and synovial fluid samples from 88 horses.
  • The effects of clinical variables such as horse workload and age on miRNA expression were evaluated.

Key Findings

  • 43 miRNAs were differentially expressed in serum; 23 were differentially expressed in synovial fluid between OA and control horses.
  • Many altered miRNAs are linked to inflammatory processes and pathways known to be involved in osteoarthritis development.
  • Serum miRNA expression was highly influenced by the horse’s workload, indicating physical activity may affect circulating miRNAs.
  • Age had a strong impact on miRNA levels in synovial fluid, suggesting age-related changes in joint microenvironment contribute to disease signatures.
  • Distinct miRNA expression patterns emerged for serum versus synovial fluid, highlighting compartment-specific biomarker profiles.
  • Among the six miRNAs selected for validation, miR-199a-3p and miR-148a stood out as promising candidates for further research into their biomarker potential.

Interpretation and Implications

  • Identifying circulating and joint-specific miRNAs associated with OA may aid in developing minimally invasive diagnostic tests for early detection of equine OA.
  • Understanding the molecular pathways influenced by these miRNAs could reveal mechanisms driving OA progression.
  • miR-199a-3p and miR-148a, in particular, merit deeper study to confirm their role as biomarkers and explore therapeutic potential.
  • Accounting for variables such as workload and age when evaluating miRNA biomarkers is important, as these factors impact miRNA expression independently of disease.
  • These findings provide a foundation for future research into equine OA diagnostics and therapeutics focused on miRNA regulation.

Summary

  • This study demonstrated that miRNA profiles in serum and synovial fluid differ between healthy and osteoarthritic horses, reflecting disease-associated molecular changes.
  • Validation in a larger cohort supports the robustness of the findings and highlights specific miRNAs as promising biomarker candidates.
  • Ultimately, this research contributes to the ongoing effort to improve diagnosis and understanding of osteoarthritis in horses through molecular biomarkers.

Cite This Article

APA
Castanheira CIGD, Taylor S, Skiöldebrand E, Rubio-Martinez LM, Hackl M, Clegg PD, Peffers MJ. (2025). Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis. Int J Mol Sci, 26(22), 11190. https://doi.org/10.3390/ijms262211190

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 26
Issue: 22
PII: 11190

Researcher Affiliations

Castanheira, Catarina I G D
  • Department of Musculoskeletal and Ageing Research, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Taylor, Sarah
  • The Royal (Dick) School of Veterinary Studies, The Roslin Institute, University of Edinburgh, Edinburgh EH8 9YL, UK.
Skiöldebrand, Eva
  • Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.
Rubio-Martinez, Luis M
  • Sussex Equine Hospital, Billingshurst Road, Ashington RH20 3BB, UK.
Hackl, Matthias
  • TAmiRNA GmbH, Ltd., 1110 Vienna, Austria.
Clegg, Peter D
  • Department of Musculoskeletal and Ageing Research, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Peffers, Mandy J
  • Department of Musculoskeletal and Ageing Research, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.

MeSH Terms

  • Animals
  • Horses
  • Osteoarthritis / genetics
  • Osteoarthritis / blood
  • Osteoarthritis / veterinary
  • Osteoarthritis / metabolism
  • Synovial Fluid / metabolism
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Horse Diseases / genetics
  • Horse Diseases / blood
  • Horse Diseases / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Male
  • Female
  • Gene Expression Profiling

Grant Funding

  • G5018 / The Horse Trust
  • MR/P020941/1 / Medical Research Council
  • 107471/Z/15/Z / Wellcome Trust

Conflict of Interest Statement

Matthias Hackl is an employee of TAmiRNA, GmBH. The remaining authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Citations

This article has been cited 1 times.
  1. Li L, Xu Z, Gao F, Xu J. Current status and future prospects of nanocarrier-mediated miRNA delivery for osteoarthritis therapy. Front Med (Lausanne) 2025;12:1728944.
    doi: 10.3389/fmed.2025.1728944pubmed: 41625748google scholar: lookup
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