Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career

Abstract

BackgroundJoint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma.ResultsThe concentrations of IL1-ß, IL-6, TNF-α in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-α in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3.Conclusions Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-α can reliably predict radiographic progression of PTOA.

Determination of reference values for cytokines and matrix metalloproteinases in the synovial fluid of horses of different ages

“…The synovial concentration of TNF-α in racehorses seems to increase after 3 years from the beginning of training (BERTUGLIA et al, 2016).…”

“…Early detection is very important for disease prevention and clinical treatment planning. A deeper understanding about the fluctuations of these biomarkers could make it possible to implement individualized therapies in the future (BERTUGLIA et al, 2016).…”

Immune response biomarkers in human and veterinary research

“…This is not only true for human immunology, but numerous examples can also be found in veterinary medicine. A good illustration of this is the study carried out by Bertuglia and colleagues, in which the kinetics of pro-inflammatory cytokines such as TNFα were associated with equine osteoarthritis (mean of ∼100 pg/ml in synovial fluid and ∼35 pg/ml in serum) [10]. Furthermore, changes in IFNα, IL-8 and TNFα have been described during classical swine fever infection (for example, peak between 3 and 8 days post-infection of IFNα reaching levels up to 1100 pg/ml) [11] and particular cytokine profiles have been associated with natural African trypanosome infections in cattle (mean of ∼280 pg/ml of IL-10 in infected cattle versus ∼150 pg/ml in uninfected animals, as well as ∼5 pg/ml of TNFα and ∼2.8 pg/ml in infected and uninfected animals, respectively) [12].…”

Ex-VivoEquine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study

“…Elevations in TNF-α and IL-1β are regularly identified within OA synovial fluid, including that of horses [17][18][19] . TNF-α and IL-1β have therefore become established experimental treatments for modelling OA pathology within in vitro and ex-vivo studies, having been used both independently and as a combined treatment [20][21][22][23][24][25][26] .…”