“One Health” in tendinopathy research: Current concepts

Abstract

Tendinopathy remains one of the most common musculoskeletal disorders affecting both human and equine athletes and presents a considerable therapeutic challenge. The following workshop report comes from the third Dorothy Havemeyer Symposium of Tendinopathy which provided a unique overview of our current understanding of both the basic science and the clinical challenges for diagnosing and treating tendinopathy in both species. Pathologically, tendon demonstrates alterations in both cellular, molecular, structural, and biomechanical features, leading to a spectrum of pathological endotypes. To develop novel interventions to manage, treat or prevent tendinopathies it is vital to understand the underlying mechanisms that lead to both tendon failure, and also regeneration and resolution of inflammation. The horse shows analogous pathology with both human Achilles tendinopathy (superficial digital flexor tendon) and intrathecal rotator cuff tears (deep digital flexor tendon tears) enabling scientists and clinicians from both medical and veterinary fields to work jointly on matching naturally occurring disease models. The experience in human medicine on the design, conduct, and impact of clinical trials has much to inform clinical trials in horses. There is a need to design appropriate studies to address clear questions, socialize the study to achieve good enrollment, and consider the significance and impact of the clinical question as well as the cost of addressing it. Because economics is often a limitation in equine medicine the use of observational studies, and specifically registries, should be given careful consideration.

Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis

“…A key feature of DSLD is acellular accumulation of proteoglycans, such as aggrecan and decorin, replacing cells and collagen bundles, suggesting disturbance to matrix homeostasis ( Halper et al 2006 , 2011 ; Schenkman et al 2009 ; Young et al 2018 ). Such features parallel tendon aging and tendinopathy in humans ( Winnicki et al 2020 ; Smith and McIlwraith 2021 ). A certain amount of proteoglycan turnover may be required to maintain normal tendon/ligament collagen assembly and matrix homeostasis by aggrecanases that are constitutively active in the tissue ( Rees et al 2009 ).…”

Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse

“…Superficial digital flexor tendon (SDFT) injuries are a severe problem that affect a large percentage of athletic and pleasure horses; often they develop recidivisms and, in the worst scenario, have to retire from competition early (9,47). In a One Health perspective, the equine could play an important role as a model for human musculoskeletal disorders because of their similarities (48)(49)(50), especially for investigating the regenerative efficacies of innovative treatments such as PRP, bone marrow aspirate (BMA), or MSCs. However, in human medicine there is a limited knowledge about the combinatory application of these therapies, which is restricted to the treatment of knee osteoarthritis (51,52) and rotator cuff rupture (53).…”

Equine Endothelial Cells Show Pro-angiogenic Behaviours in Response to FGF2 but Not VEGF-A

“…This process is important for normal tissue maintenance and repair and is disordered in disease states where endothelial dysfunction is prevalent [1]. Despite growing interest in the horse as a large animal model for a range of diseases [2][3][4][5][6][7][8][9][10][11][12][13], and the recognition that this species has utility for investigating wound healing and regenerative medicine [14][15][16][17], our understanding of equine EC biology has received minimal scientific attention.…”