Exploring the roles of snoRNA-induced ribosome heterogeneity in equine osteoarthritis.
Abstract: Osteoarthritis (OA) is a degenerative joint disease that greatly contributes to equine morbidity and poor welfare. Changes in cellular protein expression programs fuel the development and progression of OA. Small nucleolar RNAs (snoRNAs) are emerging as important regulators of OA (patho)biology. SnoRNAs are short non-coding RNAs that guide post-transcriptional modifications (PTMs) of ribosomal RNA (rRNA) nucleotides, which impact ribosome function and thus cellular protein expression programs. There is only very limited data on snoRNAs in equine OA. Unassigned: In this study, we induced OA in horses ( = 9) using a well-established equine carpal osteochondral fragment model of OA. We collected synovial fluid (SF) before (Day 0) and after OA-inducing surgery (Day 28, Day 70). Using small RNA sequencing, we then measured snoRNA levels in SF. Unassigned: We identified 229 snoRNAs across all samples of which 30 snoRNAs were significantly differentially expressed (DE) in Day 28 vs. Day 0 comparison, 22 snoRNAs in Day 70 vs. Day 0, and finally, 23 snoRNAs in Day 70 vs. Day 28. On Day 28, the majority of DE snoRNAs were upregulated when compared to Day 0. In contrast, the majority of DE snoRNAs on Day 70 were downregulated when compared to Day 0 and Day 28. Altogether, 44 snoRNAs were DE across different comparisons, the majority of which were canonical snoRNAs. We then mapped all the predicted PTMs guided by the DE snoRNAs within a 3D ribosome. Unassigned: Several of these PTMs were located within functionally important ribosomal regions. This included helices H89-H91 of peptidyl transferase center, helices H37-H39 of A-site finger and B1a ribosomal bridge, helices H70-H71, 5.8S-28S junction, and lastly, helices h14 and H95 of GTPase-associated center. Altogether, our novel data show that snoRNAs are regulated in equine OA, highlighting their potential as early molecular biomarkers and therapeutic targets. Targeting snoRNA to modulate protein synthesis in OA joints could ultimately improve outcomes for OA-affected horses.
Copyright © 2025 Chabronova, Walters, Regårdh, Jacobsen, Bundgaard, Anderson and Peffers.
Publication Date: 2025-07-10 PubMed ID: 40709001PubMed Central: PMC12288042DOI: 10.3389/fvets.2025.1562508Google Scholar: Lookup
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Summary
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The research article investigates the role of Small nucleolar RNAs (snoRNAs), in equine (horse) Osteoarthritis (OA), a disease affecting horses’ joints. The study revealed significant variations in snoRNA expression during the progression of OA, suggesting these non-coding RNAs could be potential molecular biomarkers or treatment targets for the disease.
Objective and Methodology
- The aim was to explore the role of snoRNAs in equine OA, a degenerative joint disease in horses that contributes significantly to horse morbidity and poor welfare.
- The researchers induced OA in nine horses using a recognised equine carpal osteochondral fragment model of OA.
- They then collected the synovial fluid, the clear, viscid bodily fluid found in the cavities of synovial joints, from these horses before (Day 0) and after (Day 28, Day 70) the OA-inducing surgery.
- The snoRNA levels in the collected synovial fluid were then measured using small RNA sequencing.
Key Findings
- A total of 229 snoRNAs were identified across all samples, with specific ones showing significant differential expression (DE) when compared at different stages of OA progression.
- They found 30 snoRNAs were significantly DE in Day 28 vs. Day 0 comparison, 22 snoRNAs in Day 70 vs. Day 0, and finally, 23 snoRNAs in Day 70 vs. Day 28.
- Interestingly, most of the DE snoRNAs at Day 28 were upregulated compared to Day 0. But by Day 70, most of these snoRNAs were downregulated when compared to both Day 0 and Day 28.
- The team then mapped the post-transcriptional modifications (PTMs) guided by these DE snoRNAs within a 3D ribosome and found them to be located within vital ribosomal regions.
Implications of the Study
- This pioneering data reveals that snoRNAs are regulated during the progression of equine OA. It suggests snoRNAs could be used as early molecular biomarkers for OA in horses, a significant leap in diagnosing this debilitating disease.
- Moreover, they might also serve as potential therapeutic targets, where manipulating snoRNA could regulate protein synthesis in OA joints, thereby improving outcomes for horses with OA.
Cite This Article
APA
Chabronova A, Walters M, Regårdh S, Jacobsen S, Bundgaard L, Anderson JR, Peffers MJ.
(2025).
Exploring the roles of snoRNA-induced ribosome heterogeneity in equine osteoarthritis.
Front Vet Sci, 12, 1562508.
https://doi.org/10.3389/fvets.2025.1562508 Publication
Researcher Affiliations
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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