On the road to biomarkers: developing a robust system for miRNA evaluation in equine blood and synovial fluid

Antunes, Joshua; Koch, Thomas; Koenig, Jeremy E.; Côté, Nathalie; Dubois, Marie‐Daniéla

doi:10.1016/j.joca.2019.02.165

Cited by 3 publications

(2 citation statements)

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“…Intra-articular treatment with hyaluronic acid was shown to modify miRNA expression in OA patients [ 32 ]. Although miRNA expression has not yet been investigated in equine OA, a preliminary study has recently described a reproducible method for miRNA isolation from equine synovial fluid and blood plasma [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background 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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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Biofluid miRNA research in equine OA is extremely limited. In 2019, a pilot study reported a robust repeatable methodology for miRNA isolation from equine synovial fluid and plasma [ 24 ]. The first equine study to investigate small non-coding RNA signatures in early OA of equine synovial fluid found miR-223 was significantly downregulated in synovial fluid from the early OA group compared to the controls and miR-23b was significantly upregulated [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of MicroRNA Biomarkers in Equine Distal Interphalangeal Joint Osteoarthritis

Baker

Lee

Clinton

et al. 2022

IJMS

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Osteoarthritis of the equine distal interphalangeal joint is a common cause of lameness. MicroRNAs from biofluids are promising biomarkers and therapeutic candidates. Synovial fluid samples from horses with mild and severe equine distal interphalangeal joint osteoarthritis were submitted for small RNA sequencing. The results demonstrated that miR-92a was downregulated in equine synovial fluid from horses with severe osteoarthritis and there was a significant increase in COMP, COL1A2, RUNX2 and SOX9 following miR-92a mimic treatment of equine chondrocytes in monolayer culture. This is the first equine study to evaluate the role of miR-92a in osteoarthritic chondrocytes in vitro.

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

Castanheira

Balaskas

Falls

et al. 2020

Preprint

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BackgroundOsteoarthritis 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.MethodsSmall RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic non-Thoroughbred 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.ResultsResults 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 OA and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular functions 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).ConclusionsSynovial fluid sncRNAs can 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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On the road to biomarkers: developing a robust system for miRNA evaluation in equine blood and synovial fluid

Cited by 3 publications

References 0 publications

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

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

Investigation of MicroRNA Biomarkers in Equine Distal Interphalangeal Joint Osteoarthritis

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

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