Castanheira, Catarina 
ORCID: 0000-0002-1940-7607
(2024)
Investigating the Small Non-coding RNA Profile in Equine Osteoarthritis.
PhD thesis, University of Liverpool.
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Abstract
One of the biggest challenges for equine medicine is the frequent occurrence of joint diseases, which are responsible for wastage of horses across all equestrian disciplines. Osteoarthritis is a joint disease of high prevalence whose pathophysiology remains somewhat elusive. Recent studies have shown that a dysregulation of small non-coding RNAs, such as microRNAs and small nucleolar RNAs, can contribute to joint tissue alterations, ultimately resulting in disease. The presence and stability of these molecules in multiple tissues and biofluids grants them the potential to be used as biomarkers of osteoarthritis. This thesis described some of the first studies to investigate the small non-coding RNA profile in equine osteoarthritis in synovial fluid and serum. Using small RNA sequencing, this thesis presented evidence of a pattern of differential expression of microRNAs and small nucleolar RNAs in osteoarthritic samples compared with control samples, of which eca-miR-199a-3p and eca-miR-148 warrant further investigation as potential biomarkers of osteoarthritis. It also demonstrated that age strongly influenced the expression of eca-miR-199a-3p, eca-miR-99b, eca-miR-146a-5p and eca-miR-23b in synovial fluid, and that the intensity of exercise a horse was subjected to was strongly associated with the microRNA profile in serum. Pathway analysis of all differentially expressed microRNA molecules revealed molecular involvement in inflammatory response, apoptosis, necrosis, autophagy and association with osteoarthritis pathways. Analysis of intercellular communication through extracellular vesicles in synovial fluid revealed a small set of differentially expressed small non-coding RNAs in osteoarthritic samples compared with control samples, which might contribute to osteoarthritis pathogenesis. Additionally, analysing the small non-coding RNA crosstalk through extracellular vesicles between synoviocytes and chondrocytes highlighted the importance of extracellular vesicle cargo as a mediator of joint homeostasis and disease. Overall, this thesis has demonstrated that small non-coding RNAs are promising candidates in osteoarthritis biomarker research, yet further work is needed. Characterising these molecular changes has offered valuable insights into different mechanisms of equine osteoarthritis, and it has shown that a single molecule is not likely to capture the complexity of mechanisms and biological processes implicated in this disease. While there are still challenges associated with small non-coding RNAs and extracellular vesicles being used diagnostically in a clinical setting, this study was one of the first steps towards the use of microRNAs and small nucleolar RNAs as biomarkers of equine osteoarthritis. Future studies investigating potential molecular biomarkers for equine osteoarthritis are likely to require an integrative multi-omic approach of genomic, epigenomic, transcriptomic, proteomic, metabolomic and lipidomic data.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Sep 2024 10:07 |
| Last Modified: | 18 Sep 2024 10:07 |
| DOI: | 10.17638/03182013 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3182013 |
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