Plasma and Synovial Fluid Cell-Free DNA Concentrations Following Induction of Osteoarthritis in Horses

Simple Summary Biological molecules (biomarkers) have been investigated for the diagnosis of osteoarthritis, but their use in equine patients has been limited due to their high cost and limited accuracy and practicality. New biomarkers that address these problems may aid in the early diagnosis and treatment of equine osteoarthritis. This study aimed to determine if the measurement of cell-free DNA, which circulates outside of cells, could be used for the early diagnosis of experimentally created osteoarthritis in horses. Osteoarthritis was surgically induced in 9 of 17 healthy Thoroughbred fillies; the eight remaining horses served as a comparison group without osteoarthritis. Afterwards, joint fluid and plasma samples were collected weekly for 9 weeks, and cell-free DNA concentrations were measured. Biomarker concentrations were significantly higher for joint fluid from horses with osteoarthritis than the comparison group at 4 weeks (median 1430 mu g/L and 631 mu g/L, respectively) and 9 weeks (median 1537 mu g/L and 606 mu g/L, respectively). There were no significant differences in plasma cell-free DNA concentrations between the horse with early osteoarthritis and the comparison group. Plasma cell-free DNA measurement is not sufficiently sensitive for early diagnosis of osteoarthritis, while measurement of this biomarker in joint fluid may be useful. Biomarkers for osteoarthritis (OA) in horses have been extensively investigated, but translation into clinical use has been limited due to cost, limited sensitivity, and practicality. Identifying novel biomarkers that overcome these limitations could facilitate early diagnosis and therapy. This study aimed to compare the concentrations of synovial fluid (SF) and plasma cell-free DNA (cfDNA) over time in control horses with those with induced carpal OA. Following an established model, unilateral carpal OA was induced in 9 of 17 healthy Thoroughbred fillies, while the remainder were sham-operated controls. Synovial fluid and plasma samples were obtained before induction of OA (Day 0) and weekly thereafter until Day 63, and cfDNA concentrations were determined using fluorometry. The SF cfDNA concentrations were significantly higher for OA joints than for sham-operated joints on Days 28 (median 1430 mu g/L and 631 mu g/L, respectively, p = 0.017) and 63 (median 1537 mu g/L and 606 mu g/L, respectively, p = 0.021). There were no significant differences in plasma cfDNA between the OA and the sham groups after induction of carpal OA. Plasma cfDNA measurement is not sufficiently sensitive for diagnostic purposes in this induced model of OA. Synovial fluid cfDNA measurement may be used as a biomarker to monitor early disease progression in horses with OA.

Automated summary

This study aimed to determine if the measurement of cell-free DNA could be used for the early diagnosis of osteoarthritis in horses. Osteoarthritis was induced in some horses, and joint fluid and plasma samples were collected for measurement. The results showed that the concentration of cell-free DNA in joint fluid was significantly higher in horses with osteoarthritis compared to the control group, but there were no significant differences in plasma cell-free DNA concentrations. Measurement of cell-free DNA in joint fluid may be useful for early diagnosis of osteoarthritis in horses.