Revisiting predictive biomarkers of musculoskeletal injury in thoroughbred racehorses: longitudinal study in polish population

Abstract Background High prevalence of musculoskeletal disorders in racehorses and its impact on horse welfare and racing economics call for improved measures of injury diagnosis and prevention. Serum biomarkers of bone and cartilage metabolism have previously shown promise in prediction of musculoskeletal injuries in horses. This study aimed to re-evaluate usability of the predictive serum biomarkers identified in North American Thoroughbred racehorses in a geographically distinct group of Polish Thoroughbreds. Results Serum concentrations of bone and cartilage biomarkers: osteocalcin, c-terminal telopeptide of type I collagen, total glycosaminoglycans (GAG), chondroitin sulfate epitope and c-propeptide of type II procollagen (CPII) were evaluated in the beginning and the next 3 months of one racing season in a cohort of twenty-six 2-year-old Polish racehorses. Exit criteria were diagnosis of musculoskeletal injury, leading to > 5 days off training (n = 8), or completion of 3 study months with no training interruptions (n = 18). Normalized results and matching archival data from 35 2-year-old North American racehorses was used for logistic regression analysis to identify universal predictors of injury. Mean GAG and CPII levels were lower in injured group comparing to control, which is consistent with previous findings in racehorses. These biomarkers were also identified as predictors of injury in the mixed population model. Population origin had no significant effect on predictive value of evaluated biomarkers (Wald test p = 0.137). Decreased osteocalcin and increased c-terminal telopeptide of type I collagen levels in injured horses comparing to controls were specific for Polish population and signalized disruption in bone turnover homeostasis. Conclusions Changes in serum GAG and CPII in racehorses at risk of injury appear to be similar across distinct populations while dynamics of serum bone marker is more population-specific

Donor age affects proteome composition of tenocyte-derived engineered tendon

All proteins identified by PEAKS in young and old tendon-derived TEC with correpsonding cellular sublocations defined by IPA and Matrisome Project. (XLSX 57 kb

An Evaluation of Current Preventative Measures Used in Equine Practice to Maintain Distal Forelimb Functionality: A Mini Review

Horses are used in a variety of equestrian disciplines predisposing them to musculoskeletal injury or disease including osteoarthritis and tendinopathy. As a result, a number of preventative measures are used within equine medicine and husbandry, ranging from therapeutic shoeing to the use of nutraceuticals. Despite their popularity and routine use evidence base and clinical outcomes are variable, bringing into question the efficacy of these prophylactic measures. In recent years a small number of studies have been performed examining the effect of specific strategies in order to quantify the preventative and protective claims such modalities have on joint and forelimb health. Few have robustly demonstrated a capacity to protect the limb by reducing inflammation, or promoting regenerative pathways. This review focusses on performance horses specifically, and the resounding theme that emerges in current research is the need for longitudinal studies to inform scientific conclusions surrounding single and multi-modal use. Furthermore, there is a requirement to prioritise evidence-based medicine to inform optimal clinical practice

Temporal Extracellular Vesicle Protein Changes following Intraarticular Treatment with Integrin α10β1-selected Mesenchymal Stem Cells in Equine Osteoarthritis

IntroductionEquine osteoarthritis (OA) is a heterogeneous, degenerative disease of the musculoskeletal system with multifactorial causation, characterized by a joint metabolic imbalance. Extracellular vesicles are nanoparticles involved in intracellular communication. Mesenchymal stem cell (MSC) therapy is a form of regenerative medicine that utilizes their properties to repair damaged tissues. Despite its wide use in veterinary practice, the exact mechanism of action of MSCs is not fully understood. The aim of this study was to determine the synovial fluid extracellular vesicle protein cargo following integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) treatment in an experimental model of equine osteoarthritis with longitudinal sampling.MethodsAdipose tissue derived, integrin α10-MSCs were injected intraarticularly in six horses 18 days after experimental induction of OA. Synovial fluid samples were collected at day 0, 18, 21, 28, 35, and 70. Synovial fluid was processed and extracellular vesicles were isolated and characterized. Extracellular vesicle cargo was then analyzed using data independent acquisition mass spectrometry proteomics.ResultsA total of 442 proteins were identified across all samples, with 48 proteins differentially expressed (FDR ≤ 0.05) between sham-operated control joint without MSC treatment and OA joint treated with MSCs. The most significant pathways following functional enrichment analysis of the differentially abundant protein dataset were serine endopeptidase activity (p = 0.023), complement activation (classical pathway) (p = 0.023), and collagen containing extracellular matrix (p = 0.034). Due to the lack of an OA group without MSC treatment, findings cannot be directly correlated to only MSCs.DiscussionTo date this is the first study to quantify the global extracellular vesicle proteome in synovial fluid following MSC treatment of osteoarthritis. Changes in the proteome of the synovial fluid-derived EVs following MSC injection suggest EVs may play a role in mediating the effect of cell therapy through altered joint homeostasis. This is an important step toward understanding the potential therapeutic mechanisms of MSC therapy, ultimately enabling the improvement of therapeutic efficacy