Harnessing the Horse for Human Osteoarthritis: microRNA-181a-5p Antisense Oligonucleotides in Clinically Normal Equine Fetlock Joints Are Safe and Well Tolerated.
4 affiliations
- 1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
- 2Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
- 3Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
- 4Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Abstract
Horses serve as a translational model for human osteoarthritis (OA) due to their comparable joint size, cartilage thickness, and incidence of naturally occurring disease. Overexpression of microRNA-181a-5p has been implicated in cartilage degradation in OA, and its inhibition using locked nucleic acid antisense oligonucleotides (LNA-miR-181a-5p ASOs) represents a potential therapeutic strategy. This study evaluated the safety of intraarticular (IA) LNA-miR-181a-5p ASO injection in clinically normal horse fetlock joints. Twelve horses were randomized to receive two IA injections, 28 days apart, of either low-dose [2000 µg (n = 6)] or high-dose [4000 µg (n = 6)] LNA-miR-181a-5p ASO. Over 56 days, variables assessed included physical examinations, joint assessments (effusion, circumference, temperature), lameness scores, and biofluid analyses. Physical and lameness evaluation variables remained similar to baseline and did not differ by dose (p > 0.05). Joint effusion was mildly increased in high-dose joints at Day 3 post-injection (p < 0.05), while circumference, temperature, and hematologic and biochemical variables remained similar to baseline, and did not differ by dose (p > 0.05). A transient, dose-independent increase (p < 0.05) in nucleated cell count at day 3 following each injection was observed, consistent with post-arthrocentesis inflammation. Synovial fluid IL-1β and PGE₂ concentrations did not differ across doses and timepoints (p > 0.05). Although TNF-α concentrations were greater in the high-dose group (p < 0.05), values were variable across horses, even prior to treatment. Overall, IA LNA-miR-181a-5p ASO was well tolerated in clinically normal horse fetlocks, with only transient inflammatory changes, supporting its evaluation as a potential OA therapy.
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BibTeX
@article{mccorkell2026harnessing,
title = {{Harnessing the Horse for Human Osteoarthritis: microRNA-181a-5p Antisense Oligonucleotides in Clinically Normal Equine Fetlock Joints Are Safe and Well Tolerated.}},
author = {T Connor McCorkell and Narman Mortagy and Rodrigo Munevar Luque and Thomas G Koch and Janet Beeler-Marfisi and Y Raja Rampersaud and Jonathan Lamarre and Mohit Kapoor and Judith B Koenig},
journal = {Journal of orthopaedic research : official publication of the Orthopaedic Research Society},
year = {2026},
month = oct,
doi = {10.1002/jor.70298},
url = {https://europepmc.org/article/MED/42926329},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Harnessing the Horse for Human Osteoarthritis: microRNA-181a-5p Antisense Oligonucleotides in Clinically Normal Equine Fetlock Joints Are Safe and Well Tolerated.
AU - T Connor McCorkell
AU - Narman Mortagy
AU - Rodrigo Munevar Luque
AU - Thomas G Koch
AU - Janet Beeler-Marfisi
AU - Y Raja Rampersaud
AU - Jonathan Lamarre
AU - Mohit Kapoor
AU - Judith B Koenig
PY - 2026
DA - 2026/10/30
JO - Journal of orthopaedic research : official publication of the Orthopaedic Research Society
DO - 10.1002/jor.70298
UR - https://europepmc.org/article/MED/42926329
AB - Horses serve as a translational model for human osteoarthritis (OA) due to their comparable joint size, cartilage thickness, and incidence of naturally occurring disease. Overexpression of microRNA-181a-5p has been implicated in cartilage degradation in OA, and its inhibition using locked nucleic acid antisense oligonucleotides (LNA-miR-181a-5p ASOs) represents a potential therapeutic strategy. This study evaluated the safety of intraarticular (IA) LNA-miR-181a-5p ASO injection in clinically normal horse fetlock joints. Twelve horses were randomized to receive two IA injections, 28 days apart, of either low-dose [2000 µg (n = 6)] or high-dose [4000 µg (n = 6)] LNA-miR-181a-5p ASO. Over 56 days, variables assessed included physical examinations, joint assessments (effusion, circumference, temperature), lameness scores, and biofluid analyses. Physical and lameness evaluation variables remained similar to baseline and did not differ by dose (p > 0.05). Joint effusion was mildly increased in high-dose joints at Day 3 post-injection (p < 0.05), while circumference, temperature, and hematologic and biochemical variables remained similar to baseline, and did not differ by dose (p > 0.05). A transient, dose-independent increase (p < 0.05) in nucleated cell count at day 3 following each injection was observed, consistent with post-arthrocentesis inflammation. Synovial fluid IL-1β and PGE₂ concentrations did not differ across doses and timepoints (p > 0.05). Although TNF-α concentrations were greater in the high-dose group (p < 0.05), values were variable across horses, even prior to treatment. Overall, IA LNA-miR-181a-5p ASO was well tolerated in clinically normal horse fetlocks, with only transient inflammatory changes, supporting its evaluation as a potential OA therapy.
SN - 0736-0266
SN - 1554-527X
ER -