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BMC veterinary research2021; 17(1); 26; doi: 10.1186/s12917-020-02707-7

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis.

Abstract: Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potentially provide early biomarkers. Methods: Small RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic horses. A group of differentially expressed sncRNAs was selected for further validation through qRT-PCR using an independent cohort of synovial fluid samples from control and early osteoarthritic horses. Bioinformatic analysis was performed in order to identify putative targets of the differentially expressed microRNAs and to explore potential associations with specific biological processes. Results: Results revealed 22 differentially expressed sncRNAs including 13 microRNAs; miR-10a, miR-223, let7a, miR-99a, miR-23b, miR-378, miR-143 (and six novel microRNAs), four small nuclear RNAs; U2, U5, U11, U12, three small nucleolar RNAs; U13, snoR38, snord96, and one small cajal body-specific RNA; scarna3. Five sncRNAs were validated; miR-223 was significantly reduced in early osteoarthritis and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular actions deduced by the differentially expressed microRNAs included apoptosis (P < 0.0003), necrosis (P < 0.0009), autophagy (P < 0.0007) and inflammation (P < 0.00001). A conservatively filtered list of 57 messenger RNA targets was obtained; the top biological processes associated were regulation of cell population proliferation (P < 0.000001), cellular response to chemical stimulus (P < 0.000001) and cell surface receptor signalling pathway (P < 0.000001). Conclusions: Synovial fluid sncRNAs may be used as molecular biomarkers for early disease in equine osteoarthritic joints. The biological processes they regulate may play an important role in understanding early osteoarthritis pathogenesis. Characterising these dynamic molecular changes could provide novel insights on the process and mechanism of early osteoarthritis development and is critical for the development of new therapeutic approaches.
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Publication Date: 2021-01-09 PubMed ID: 33422071PubMed Central: PMC7796526DOI: 10.1186/s12917-020-02707-7Google Scholar: Lookup
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  • Journal Article

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 identifying early signs of osteoarthritis in horses using small non-coding RNAs (sncRNAs) found in synovial fluid and how their expression changes may be used to understand disease progression better. This knowledge may guide the development of effective therapeutic methodologies.

Methodology

  • The study compares small RNA sequencing from the synovial fluid of horses’ metacarpophalangeal joints, both from those with early osteoarthritis and controls.
  • The differentially expressed sncRNAs were further validated using an independent cohort of synovial fluid samples in the same conditions.
  • Through bioinformatics analysis, the researchers aimed to identify the potential actions of these differentially expressed miRNAs and how they relate to particular biological processes.

Findings

  • They identified 22 differentially expressed sncRNAs, including 13 specific microRNAs and other RNA types.
  • Five sncRNAs were validated – miR-223, which was significantly lower in early osteoarthritis, and four others that were significantly higher, including miR-23b, let-7a-2, snord96A, and snord13.
  • The differential expression could infer significant cellular actions such as apoptosis, necrosis, autophagy, and inflammation.
  • A list of 57 mRNA targets was obtained. The top associated biological processes were regulation of cell population proliferation, cellular response to chemical stimulus, and cell surface receptor signaling pathways.

Conclusion

  • These results suggest that sncRNAs in synovial fluid could be used as potential biomarkers to detect early osteoarthritis in equine joints.
  • The biological processes they regulate may provide vital insight into the pathogenesis of early onset osteoarthritis.
  • Better understanding of these molecular changes could offer novel insights into the development process and mechanism of early osteoarthritis and could be crucial for developing new therapeutic strategies.

Cite This Article

APA
Castanheira C, Balaskas P, Falls C, Ashraf-Kharaz Y, Clegg P, Burke K, Fang Y, Dyer P, Welting TJM, Peffers MJ. (2021). Equine synovial fluid small non-coding RNA signatures in early osteoarthritis. BMC Vet Res, 17(1), 26. https://doi.org/10.1186/s12917-020-02707-7

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 17
Issue: 1
Pages: 26

Researcher Affiliations

Castanheira, Catarina
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK. C.Castanheira@liverpool.ac.uk.
Balaskas, Panagiotis
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Falls, Charlotte
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Ashraf-Kharaz, Yalda
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Clegg, Peter
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Burke, Kim
  • Institute of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK.
Fang, Yongxiang
  • Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK.
Dyer, Philip
  • Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L7 3EA, UK.
Welting, Tim J M
  • Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, AZ, 6202, The Netherlands.
Peffers, Mandy J
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.

MeSH Terms

  • Animals
  • Biomarkers
  • Horse Diseases / diagnosis
  • Horses
  • Osteoarthritis / diagnosis
  • Osteoarthritis / metabolism
  • Osteoarthritis / veterinary
  • RNA, Small Untranslated / metabolism
  • Synovial Fluid

Grant Funding

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

Conflict of Interest Statement

The authors declare no competing interests.

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