Orthobiologic use for equine joint disease
Type of DegreePhD Dissertation
General Veterinary Medicine
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Osteoarthritis (OA) is the leading cause of musculoskeletal disability in people and Horses. There is a critical need for better understanding of new therapeutics and their effects on the disease. Orthobiologics are biologically derived products processed and used to promote repair or regeneration of injured musculoskeletal tissues. The overarching aim of this body of work was to investigate the use of orthobiologic therapies by equine veterinarians and gain a better understanding of the effects of certain orthobiologic therapies such as autologous conditions serum (ACS) and autologous protein solution (APS) compared to corticosteroids [triamcinolone acetonide (TA)]. The first presented study is a survey sent to national and international equine practitioners to evaluate their use of orthobiologics. Orthobiologic use has increased among practitioners, with an observed preference for blood-based, mostly point- of-care products to treat acute joint-related pathology compared to past years. However, corticosteroids remain the most widely used intra-articular therapeutic among equine practitioners. In vitro studies were completed using synovium and cartilage co-culture systems stimulated with IL-1β. The first presented study evaluated the effects of 10% equine serum supplementation compared to serum-free media for culture of synovial tissues. Supplementation of the media with 10% equine serum provided chondroprotective effects more evident over long-term (> 9 days) culture. Based on the results of the study using serum-free media to study OA in vitro is recommended. Using the same in vitro model, the effects of ACS and APS obtained from the same horse were compared to a common intra-articular treatment, TA. PGE2 concentrations in media were significantly reduced following treatment with APS and ACS, while TA did not reduce PGE2 significantly. The effect of ACS and TA were also compared in a in vivo synovitis model stimulated with IL-1β. In this study, intra-articular injection of IL-1β with ACS produced the highest total nucleated cell count within synovial fluid, but surprisingly the lowest lameness scores compared to IL-1β alone or IL-1β + TA. The PGE2 concentration in synovial fluid was lower after ACS and TA administration with IL-1β when compared to IL-1β alone. However, TA with IL-1β caused an increase in cartilage metabolism measured by increased glycosaminoglycans in the synovial fluid compared to PBS, IL-1β alone, ACS alone or in combination with IL-1β. Results provide evidence that orthobiologics may offer an improved strategy for horses with naturally occurring OA, compared to the standard treatment of TA, by decreasing the concentration of PGE2, one of the most important pro-inflammatory proteins in OA disease.