The equine model refers to the use of horses as a biological model in scientific research to study various physiological and pathological processes. Horses are utilized in research due to their unique physiological characteristics, which can parallel certain aspects of human health and disease. This model is applied in studies ranging from musculoskeletal disorders and respiratory diseases to metabolic syndromes and reproductive health. Research involving equine models often investigates disease mechanisms, therapeutic interventions, and preventative strategies. This page gathers peer-reviewed research studies and scholarly articles that explore the application, benefits, and limitations of using horses as models in scientific research, providing insights into equine and comparative biomedical studies.
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. The effects of recombinant interleukin-1β (rIL-1β) have been described for the middle carpal joint (MCJ). However, we are unaware of any studies that have described the cytological response of the tibiotarsal joint (TTJ) to rIL-1β or compared the clinical and cytological responses of the MCJ to the TTJ following the administration of intra-articular rIL-1β. Such information is critical for researchers planning to use rIL-1β to create acute synovitis models in horses. To compare the clinical and cytological responses of the MCJ to the TTJ following administration of intra-articular rIL-1...
Harman RM, He MK, Zhang S, VAN DE Walle GR.Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)-secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote woun...
Baker DL, Powers JG, Ransom JI, McCann BE, Oehler MW, Bruemmer JE, Galloway NL, Eckery DC, Nett TM.Wildlife and humans are increasingly competing for resources worldwide, and a diverse, innovative, and effective set of management tools is needed. Controlling abundance of wildlife species that are simultaneously protected, abundant, competitive for resources, and in conflict with some stakeholders but beloved by others, is a daunting challenge. Free-ranging horses (Equus caballus) present such a conundrum and managers struggle for effective tools for regulating their abundance. Controlling reproduction of female horses presents a potential alternative. During 2009-2017, we determined the lon...
Ongchai S, Somnoo O, Kongdang P, Peansukmanee S, Tangyuenyong S.We investigated the effect of transforming growth factor beta 1 (TGF-β1) on equine hyaluronan synthase 2 () gene expression and hyaluronan (HA) synthesis in culture models of articular chondrocytes. Equine chondrocytes were treated with TGF-β1 at different concentrations and times in monolayer cultures. In three-dimensional cultures, chondrocyte-seeded gelatin scaffolds were cultured in chondrogenic media containing 10 ng/mL of TGF-β1. The amounts of HA in conditioned media and in scaffolds were determined by enzyme-linked immunosorbent assays. mRNA expression was analyzed by semi-quantita...
Ahrberg AB, Horstmeier C, Berner D, Brehm W, Gittel C, Hillmann A, Josten C, Rossi G, Schubert S, Winter K, Burk J.Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods: Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or seru...
Sladek S, Kearney C, Crean D, Brama PAJ, Tajber L, Fawcett K, Labberte MC, Leggett B, Brayden DJ.Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions ...
Watson Levings RS, Smith AD, Broome TA, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA....The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 10 viral genomes was previously identified, which elevated the steady state levels of eqIL-1R...
Zayed M, Newby S, Misk N, Donnell R, Dhar M.Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from t...
Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA....Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produc...
Bundgaard L, Sørensen MA, Nilsson T, Salling E, Jacobsen S.In the last decades, a well-established equine wound model has been used to study fibroproliferative wound healing disorders. The aim of this study was to characterize the degree of discomfort of wounding and sampling in an equine excisional wound model by evaluating systemic and local inflammatory responses and signs of pain. A total of 12 cutaneous wounds, three on each shoulder and each metatarsus, were created in a standing surgical procedure. Wounds were biopsied on days 2, 4, 7, 14, 21, and 28 after surgery. Clinical parameters (rectal temperature, heart rate, respiratory frequency) and ...
Conley AJ, Scholtz EL, Legacki EL, Corbin CJ, Knych HK, Dujovne GD, Ball BA, Moeller BC, Stanley SD. and evidence indicates that the bioactive, 5α-reduced progesterone metabolite, 5α-dihydroprogesterone (DHP) is synthesized in the placenta, supporting equine pregnancy, but its appearance in early pregnancy argues for other sites of synthesis also. It remains unknown if DHP circulates at relevant concentrations in cyclic mares and, if so, does synthesis involve the non-pregnant uterus? Jugular blood was drawn daily from cyclic mares ( = 5). Additionally, ovariectomized mares (OVX) and geldings were administered progesterone (300 mg) intramuscularly. Blood was drawn before and after t...
Ghasemi S, Sardari K, Mirshokraei P, Hassanpour H.Application of synthetic matrix metalloproteinases (MMPs) inhibitors, such as doxycycline is one of the possible therapeutic options for osteoarthritis. However, little is known about the protective mechanism of doxycycline in equine models on MMPs inhibitors as well as on serum amyloid A (SAA) gene expression. This study investigated the effects of doxycycline on mRNA expression of MMP-1, MMP-2, MMP-9, MMP-13, and SAA of equine fibroblast-like synoviocytes (FLSs). The FLSs were established from synovial fluids of clinically normal metacarpophalangeal joints of 6 skeletally mature horses. The ...
Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, Korthagen NM.Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple L...
Rotter Sopasakis V, Wickelgren R, Sukonina V, Brantsing C, Svala E, Hansson E, Enerbäck S, Lindahl A, Skiöldebrand E.Chondrocytes are responsible for remodeling and maintaining the structural and functional integrity of the cartilage extracellular matrix. Because of the absence of a vascular supply, chondrocytes survive in a relatively hypoxic environment and thus have limited regenerative capacity during conditions of cellular stress associated with inflammation and matrix degradation, such as osteoarthritis (OA). Glucose is essential to sustain chondrocyte metabolism and is a precursor for key matrix components. In this study, we investigated the importance of glucose as a fuel source for matrix repair dur...
Fortuna PRJ, Bielefeldt-Ohmann H, Ovchinnikov DA, Wolvetang EJ, Whitworth DJ.Horses are susceptible to a number of neurotropic viruses, including West Nile virus (WNV), which is a pathogen of global significance in both horses and humans. However, there are no in vitro models with which to study infectious neuropathic diseases in the horse. In an effort to redress this, we have generated neurons from equine induced pluripotent stem cells (equiPSCs) that express a range of cortical neuron-specific markers, in addition to the membrane-bound ligand ephrin B3, which plays an important role in axon guidance as well as functioning as the receptor through which henipaviruses,...
Salonius E, Rieppo L, Nissi MJ, Pulkkinen HJ, Brommer H, Brünott A, Silvast TS, Van Weeren PR, Muhonen V, Brama PAJ, Kiviranta I.The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, ...
Salgado RM, Brom-de-Luna JG, Resende HL, Canesin HS, Hinrichs K.The aim of this study was to evaluate the differential effects of conventional and Piezo-driven ICSI on blastocyst development, and on sperm component remodeling and oocyte activation, in an equine model. Methods: In vitro-matured equine oocytes underwent conventional (Conv) or Piezo ICSI, the latter utilizing fluorocarbon ballast. Blastocyst development was compared between treatments to validate the model. Then, oocytes were fixed at 0, 6, or 18 h after injection, and stained for the sperm tail, acrosome, oocyte cortical granules, and chromatin. These parameters were compared between inject...
Seluanov A, Gladyshev VN, Vijg J, Gorbunova V.Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly and are highly prone to cancer. They have been very useful for modelling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique traits of very high value to humans, such as cancer resistance and longevity. In recent years, several...
The ultra long-acting β -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combina...
Trachsel DS, Tejada MA, Groesfjeld Christensen V, Pedersen PJ, Kanters JK, Buhl R, Calloe K, Klaerke DA.The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the K 11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim-sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine...
Rivas F, Zahid OK, Reesink HL, Peal BT, Nixon AJ, DeAngelis PL, Skardal A, Rahbar E, Hall AR.Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA w...
Ribitsch I, Peham C, Ade N, Dürr J, Handschuh S, Schramel JP, Vogl C, Walles H, Egerbacher M, Jenner F.Meniscal pathologies are among the most common injuries of the femorotibial joint in both human and equine patients. Pathological forces and ensuing injuries of the cranial horn of the equine medial meniscus are considered analogous to those observed in the human posterior medial horn. Biomechanical properties of human menisci are site- and depth- specific. However, the influence of equine meniscus topography and composition on its biomechanical properties is yet unknown. A better understanding of equine meniscus composition and biomechanics could advance not only veterinary therapies for meni...
Duan W, Chen C, Haque M, Hayes D, Lopez MJ.Use of bioscaffolds to direct osteogenic differentiation of adult multipotent stromal cells (MSCs) without exogenous proteins is a contemporary approach to bone regeneration. Identification of in vivo osteogenic contributions of exogenous MSCs on bioscaffolds after long-term implantation is vital to understanding cell persistence and effect duration. This study was designed to quantify in vivo equine MSC osteogenesis on synthetic polymer scaffolds with distinct mineral combinations 9 weeks after implantation in a murine model. Cryopreserved, passage (P)1, equine bone marrow-derived MSCs (BMSC)...
DeBoer ML, Martinson KM, Pampusch MS, Hansen AM, Wells SM, Ward C, Hathaway M.Leucine has been shown to stimulate the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway which plays numerous key regulatory roles in cell growth, survival, and metabolism including protein synthesis in a number of species. However, previous work with equine satellite cells has suggested distinct species differences in regards to physiological effects and the magnitude of responses to growth factors and regulators. Because there is limited research available regarding the role of leucine in regulating equine skeletal muscle protein synthesis, the objective of this study was t...
Desancé M, Contentin R, Bertoni L, Gomez-Leduc T, Branly T, Jacquet S, Betsch JM, Batho A, Legendre F, Audigié F, Galéra P, Demoor M.Cartilage engineering is a new strategy for the treatment of cartilage damage due to osteoarthritis or trauma in humans. Racehorses are exposed to the same type of cartilage damage and the anatomical, cellular, and biochemical properties of their cartilage are comparable to those of human cartilage, making the horse an excellent model for the development of cartilage engineering. Human mesenchymal stem cells (MSCs) differentiated into chondrocytes with chondrogenic factors in a biomaterial appears to be a promising therapeutic approach for direct implantation and cartilage repair. Here, we cha...
Bradbery AN, Coverdale JA, Vernon KL, Leatherwood JL, Arnold CE, Dabareiner RA, Kahn MK, Millican AA, Welsh TH.Seventeen yearling Quarter Horses were used in a randomized complete block design for a 56-d trial to determine ability of dietary CLA to mitigate joint inflammation and alter cartilage turnover following an inflammatory insult. Horses were blocked by age, sex, and BW, and randomly assigned to dietary treatments consisting of commercial concentrate offered at 1% BW (as-fed) supplemented with either 1% soybean oil (CON; n = 6), 0.5% soybean oil and 0.5% CLA (LOW; n = 5; 55% purity; Lutalin, BASF Corp., Florham Park, NJ), or 1% CLA (HIGH; n = 6) top-dressed daily. Horses were fed individually ev...
Chu CR, Fortier LA, Williams A, Payne KA, McCarrel TM, Bowers ME, Jaramillo D.Microfracture is commonly performed for cartilage repair but usually results in fibrocartilage. Microfracture augmented by autologous bone marrow concentrate (BMC) was previously shown to yield structurally superior cartilage repairs in an equine model compared with microfracture alone. The current study was performed to test the hypothesis that autologous BMC without concomitant microfracture improves cartilage repair compared with microfracture alone. Methods: Autologous sternal bone marrow aspirate (BMA) was concentrated using a commercial system. Cells from BMC were evaluated for chondroge...
Labens R, Daniel C, Hall S, Xia XR, Schwarz T.Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton lase...
Ma TW, Li Y, Wang GY, Li XR, Jiang RL, Song XP, Zhang ZH, Bai H, Li X, Gao L.The study aimed to clarify the changes in the concentration of inflammatory mediators, proteases, and cartilage degradation biomarkers in the synovial fluid of joints in an equine osteoarthritis model. Methods: Osteoarthritis was induced in eight Mongolian horses by a sterile intra-articular injection of amphotericin B, which was injected into the left carpal joint in a dose of 2 mL (25 mg/mL). The control group comprised five horses which were injected with an equal dose of sterile physiological saline into the left carpal joint. Synovial fluid was obtained at baseline and every week after in...
Pacholewska A, Kraft MF, Gerber V, Jagannathan V.MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression ana...
Groppelli E, Tuthill TJ, Rowlands DJ.Equine rhinitis A virus (ERAV) is genetically closely related to foot-and-mouth disease virus (FMDV), and both are now classified within the genus Aphthovirus of the family Picornaviridae. For disease security reasons, FMDV can be handled only in high-containment facilities, but these constraints do not apply to ERAV, making it an attractive alternative for the study of aphthovirus biology. Here, we show, using immunofluorescence, pharmacological agents, and dominant negative inhibitors, that ERAV entry occurs (as for FMDV) via clathrin-mediated endocytosis and acidification of early endosomes...
Kaynarcalidan O, Oğuzoğlu TÇ.Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation ...
Frisbie DD, McIlwraith CW, Kawcak CE, Werpy NM.A randomized blinded placebo controlled trial was conducted to assess the clinical, biochemical and histological effects of a hyaluronan, sodium chondroitin sulfate and N-acetyl-D-glucosamine combination (PG) administered through an intra-articular (IA) route for the treatment of osteoarthritis (OA) at the time of injury. OA was induced in one carpal joint of each of 16 horses. Horses were designated placebo or IA PG treated. All horses were treated with 125 mg amikacin sulfate IA and 5 mL physiological saline in the middle carpal joint bilaterally on study Days 0 (after induction of OA), 7, 1...
Hoerdemann M, Smith RL, Hosgood G.To establish and compare the onset and duration of action of 2 local anesthetics based on objective lameness and skin sensitivity assessment. Methods: Interventional crossover experimental trial with balanced randomization. Methods: Eight horses. Methods: Reversible forelimb lameness was induced in 8 horses. A palmar digital nerve block (PDNB) was applied with mepivacaine or lidocaine (both 2%). Quantitative lameness and skin sensitivity data were collected with an inertial sensor system and a force gauge, respectively. The times to lameness resolution/skin desensitization (T1), consistent lam...
Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA.Improving the ability of DNA-based vaccines to induce potent Type1/Th1 responses against intracellular pathogens in large outbred species is essential. Rhodoccocus equi and equine infectious anemia virus (EIAV) are two naturally occurring equine pathogens that also serve as important large animal models of neonatal immunity and lentiviral immune control. Neonates present a unique challenge for immunization due to their diminished immunologic capabilities and apparent Th2 bias. In an effort to augment R. equi- and EIAV-specific Th1 responses induced by DNA vaccination, we hypothesized that a du...
Tallmadge RL, Tseng CT, King RA, Felippe MJ.Humoral immunity is a critical component of the immune system that is established during fetal life and expands upon exposure to pathogens. The extensive humoral immune response repertoire is generated in large part via immunoglobulin (Ig) heavy chain variable region diversity. The horse is a useful model to study the development of humoral diversity because the placenta does not transfer maternal antibodies; therefore, Igs detected in the fetus and pre-suckle neonate were generated in utero. The goal of this study was to compare the equine fetal Ig VDJ repertoire to that of neonatal, foal, an...
Fortuna PRJ, Bielefeldt-Ohmann H, Ovchinnikov DA, Wolvetang EJ, Whitworth DJ.Horses are susceptible to a number of neurotropic viruses, including West Nile virus (WNV), which is a pathogen of global significance in both horses and humans. However, there are no in vitro models with which to study infectious neuropathic diseases in the horse. In an effort to redress this, we have generated neurons from equine induced pluripotent stem cells (equiPSCs) that express a range of cortical neuron-specific markers, in addition to the membrane-bound ligand ephrin B3, which plays an important role in axon guidance as well as functioning as the receptor through which henipaviruses,...
Marlo TL, Giuliano EA, Sharma A, Mohan RR.To develop an ex vivo equine corneal organ culture model. Specifically, to assess the equine cornea's extracellular matrix and cellularity after 7 days using two different culture techniques: either (i) immersion system or (ii) air/liquid interface system, to determine the best ex vivo equine corneal model. Methods: Fourteen healthy equine corneas of various breeds. Methods: Equine corneas with 2 mm of perilimbal sclera were freshly harvested from 7 horses undergoing humane euthanasia. One corneal-scleral ring (CSR) from each horse was randomly placed in the (i) immersion condition organ cultu...
Buss DG, Sharma A, Giuliano EA, Mohan RR.Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in vitro model. Methods: An in vitro model of equine corneal fibroblast (ECF) developed was used. The ECF or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFbeta1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Deeg CA.Equine recurrent uveitis (ERU) is a wide spread disease of the eye, which is the main cause for blindness in horses worldwide. Meanwhile, ERU is also accepted as the only reliable spontaneous model for human autoimmune uveitis. We identified and characterized novel autoantigens by analyzing the autoantibody-binding pattern from ERU cases to the retinal proteome. Cellular retinaldehyde-binding protein (CRALBP) and malate dehydrogenase (MDH) were detected as novel ERU autoantigens by this approach. B- and T-cell autoreactivity was detected to both autoantigens in ERU cases. The evaluation of the...
Fingerhut L, Yücel L, Strutzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N.Equine recurrent uveitis (ERU) is a common ocular disease of horses and described as a model for human autoimmune uveitis. This immune-mediated, inflammatory condition progressively destroys the eye, ultimately leading to blindness. Genetic and autoimmune factors, next to infections with Leptospira, are discussed as key factors in the pathogenesis. Furthermore, a release of neutrophil extracellular traps (NETs) by activated neutrophils is involved. NETs are composed of decondensed chromatin and proteins that can immobilize invading pathogens. However, if NETs accumulate, they can contribute to...
Chang HT, Rumbeiha WK, Patterson JS, Puschner B, Knight AP.Chronic ingestion of yellow star thistle (Centaurea solstitialis) or Russian knapweed (Acroptilon repens) causes nigropallidal encephalomalacia (NPE) in horses with an abrupt onset of neurologic signs characterized by dystonia of lips and tongue, inability to prehend food, depression, and locomotor deficits. The objectives of this study were to reexamine the pathologic alterations of NPE and to conduct an immunohistochemistry study using antibodies to tyrosine hydroxylase and α-synuclein, to determine whether NPE brains show histopathologic features resembling those in human Parkinson disease...
Betteridge KJ.Carl Hartman's title of 47 years ago is invoked in tribute to his first recovery of a bovine embryo 30 years before that, and his legacy of an emphasis on the value of descriptive and comparative studies in reproductive biology. The horse's qualification as a farm animal has waned since those times but, in a conference understandably dominated by research in ruminants and pigs, there are lessons to be learned from some peculiarities of equine embryonic development. Morphological and physiological features of the conceptus and its interaction with its environment during the first month of pregn...
McCarty CA, Thomason JJ, Gordon KD, Burkhart TA, Milner JS, Holdsworth DW.To assess whether the transient stresses of foot impact with the ground are similar to those found during midstance loading and if the location of high stress correlate with the sites most commonly associated with mechanically induced osteoarthritis (OA). We compared impact stresses in subchondral bone between two subject-specific, three-dimensional, finite-element models of the equine metacarpophalangeal (MCP) joint-one with advanced OA and one healthy, and with similar published data on the stresses that occur at midstance. Methods: Two right MCP joints (third metacarpal and proximal phalanx...
Rautiainen J, Lehto LJ, Tiitu V, Kiekara O, Pulkkinen H, Brünott A, van Weeren R, Brommer H, Brama PA, Ellermann J, Kiviranta I, Nieminen MT....To evaluate the status of articular cartilage and bone in an equine model of spontaneous repair by using the sweep imaging with Fourier transform (SWIFT) magnetic resonance (MR) imaging technique. Methods: Experiments were approved by the Utrecht University Animal Ethics Committee. Six-millimeter-diameter chondral (n = 5) and osteochondral (n = 5, 3-4 mm deep into subchondral bone) defects were created in the intercarpal joints of seven 2-year-old horses and examined with SWIFT at 9.4 T after spontaneous healing for 12 months. Conventional T2 maps and gradient-echo images were obtained for com...
Herr S, Huchzermeyer HF, Te Brugge LA, Williamson CC, Roos JA, Schiele GJ.The same techniques may be used in the complement fixation test (CFT) for the serological diagnosis of bovine brucellosis, Johne's disease (paratuberculosis), dourine, equine piroplasmosis and Q fever (caused by Coxiella burnetii). The reproducibility of results is excellent, falling for the most part within the twofold range and never exceeding the fourfold range. Agreement with other laboratories is excellent (i.e. within twofold) in the case of brucellosis and equine piroplasmosis antibody titres. A good correlation between the occurrence of the disease and serological reactions is found on...
Redekopp C, Irvine CH, Donald RA, Livesey JH, Sadler W, Nicholls MG, Alexander SL, Evans MJ.Plasma ACTH, arginine vasopressin (AVP), and catecholamines were measured at 5-min intervals in the pituitary venous effluent of the unanesthetized horse. Pulses of ACTH and AVP were found to be surprisingly brief (usually of less than 10-min duration) and frequent (averaging between 15-25 min). A highly significant relationship in the changes in concentration of these two hormones was demonstrated (P less than 0.0002) both at rest and after a mild hypoglycemic stimulus. Although there was also a significant correlation (P less than 0.005) between simultaneous plasma ACTH and AVP values the pu...
Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF.Autologous protein solution (APS) has been used anecdotally for intralesional treatment of tendon and ligament injuries, however, its use in these injuries has never been studied . Our objective was to evaluate the effect of APS on tendon healing in an equine superficial digital flexor (SDF) tendonitis model. We hypothesized intralesional injection of APS would result in superior structural and biomechanical healing. SDF tendonitis was induced in both forelimbs of eight horses using collagenase injection. One forelimb was randomly assigned to receive an intralesional injection of APS, while th...
De Santis T, Casavola V, Reshkin SJ, Guerra L, Ambruosi B, Fiandanese N, Dalbies-Tran R, Goudet G, Dell'Aquila ME.The extracellular calcium-sensing receptor (CASR) plays an important role in cells involved in calcium (Ca2+) homeostasis by directly sensing changes in the extracellular Ca2+ ion concentration. We previously reported the localization and quantitative expression of CASR protein in human oocytes. In this study, we examined the expression and the functional role of CASR during oocyte meiotic maturation in a large mammal animal model, the horse. As in humans, CASR protein was found to be expressed in equine oocytes and cumulus cells. Western-blot analysis revealed a single 130 kDa band in denuded...
Verhaar N, Pfarrer C, Neudeck S, König K, Rohn K, Twele L, Kästner S.Pharmacological preconditioning of dexmedetomidine on small intestinal ischaemia/reperfusion injury has been reported in different animal models including horses. Objective: The objective was to assess if xylazine and lidocaine have a preconditioning effect in an experimental model of equine jejunal ischaemia. Methods: Terminal in vivo experiment. Methods: Ten horses under general anaesthesia were either preconditioned with xylazine (group X; n = 5) or lidocaine (group L; n = 5). A historical untreated control group (group C; n = 5) was used for comparison. An established experimental mo...
Gornik K, Moore P, Figueiredo M, Vandenplas M.Human corneal cells have detectable levels of TLRs 1-10. TLRs 2 and 4 are the major corneal receptors, recognizing the PAMPs associated with fungal invasion in humans. The conjunctiva and limbus contain TLRs 2, 4, and 9. Our purpose was to determine the expression of TLRs 2, 3, 4, 6, 9, and MD-2 in the normal equine cornea, conjunctiva, and limbus. Methods: Corneal, limbal, and conjunctival tissues were collected from seven euthanized horses having no evidence of ocular disease. RNA extraction with DNase-1 digestion was performed followed by RT-PCR to determine expression of TLRs 2, 3, 4, 6, 9...
Pavulraj S, Bera BC, Joshi A, Anand T, Virmani M, Vaid RK, Shanmugasundaram K, Gulati BR, Rajukumar K, Singh R, Misri J, Singh RK, Tripathi BN....Equine influenza viruses (EIV)-H3N8 continue to circulate in equine population throughout the world. They evolve by the process of antigenic drift that leads to substantial change in the antigenicity of the virus, thereby necessitating substitution of virus strain in the vaccines. This requires frequent testing of the new vaccines in the in vivo system; however, lack of an appropriate laboratory animal challenge model for testing protective efficacy of equine influenza vaccine candidates hinders the screening of new vaccines and other therapeutic approaches. In the present investigation, BALB/...
Eizema K, van den Burg M, Kiri A, Dingboom EG, van Oudheusden H, Goldspink G, Weijs WA.The horse is one of the few animals kept and bred for its athletic performance and is therefore an interesting model for human sports performance. The regulation of the development of equine locomotion in the first year of life, and the influence of early training on later performance, are largely unknown. The major structural protein in skeletal muscle, myosin heavy-chain (MyHC), is believed to be primarily transcriptionally controlled. To investigate the expression of the MyHC genes at the transcriptional level, we isolated cDNAs encoding the equine MyHC isoforms type 1 (slow), type 2a (fast...
Aguiar C, Theoret C, Smith O, Segura M, Lemire P, Smith LC.Induced pluripotent stem cells (iPSC) have brought immense hope to cellular therapy and regenerative medicine. However, the antigenicity of iPSC has not been well documented and remains a hurdle for clinical applications. Expression of major histocompatibility complex (MHC) molecules by human and murine iPSC is downregulated, making these cells potentially safe for transplantation. No such data are available for any large animal model. Objective: To measure expression of MHC molecules on equine iPSC (eiPSC) and describe their antigenicity using intradermal testing. The hypothesis was that allo...
Hauck SM, Lepper MF, Hertl M, Sekundo W, Deeg CA.Equine recurrent uveitis is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for...
Gebremedhn S, Gad A, Ishak GM, Menjivar NG, Gastal MO, Feugang JM, Prochazka R, Tesfaye D, Gastal EL.Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development, partially mediated by extracellular vesicles (EVs) encapsulated with microRNAs (miRNAs) and present in the follicular fluid (FF). Here, we aimed to decipher the dynamics of the miRNAs in EVs from e...
Vinther AM, Skovgaard K, Heegaard PM, Andersen PH.In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic inflammation ...
Perrier M, Lu Y, Nemke B, Kobayashi H, Peterson A, Markel M.To compare the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)/calcium phosphate (CP) to autogenous cancellous bone graft (CBG) and to no treatment on bone healing, in surgically induced osteotomies and ostectomies of the accessory metatarsal bones in an equine model. Methods: Experimental. Methods: Adult horses (n=9). Methods: Segmental ostectomies of the second metatarsal bone (MT2) and osteotomies of the fourth metatarsal bone (MT4) were performed bilaterally in 9 horses. There were a total of 35 defects (1 MT4 was previously fractured) created and supplemented randomly...
Lee CM, Kisiday JD, McIlwraith CW, Grodzinsky AJ, Frisbie DD.To develop an in vitro model of cartilage injury in full-thickness equine cartilage specimens that can be used to simulate in vivo disease and evaluate treatment efficacy. Methods: 15 full-thickness cartilage explants from the trochlear ridges of the distal aspect of the femur from each of 6 adult horses that had died from reasons unrelated to the musculoskeletal system. Methods: To simulate injury, cartilage explants were subjected to single-impact uniaxial compression to 50%, 60%, 70%, or 80% strain at a rate of 100% strain/s. Other explants were left uninjured (control specimens). All speci...
