Joint health in horses involves the study of anatomical structures such as cartilage, synovial fluid, ligaments, and bones that contribute to the function and mobility of equine joints. Research in this area focuses on understanding the physiology of equine joints, the mechanisms of joint disorders, and the effects of wear and tear over time. Common joint issues in horses include osteoarthritis, synovitis, and joint effusion, which can impact performance and quality of life. Diagnostic techniques often involve imaging, synovial fluid analysis, and clinical evaluation to assess joint condition. This page compiles peer-reviewed research studies and scholarly articles that explore the anatomy, pathology, diagnostics, and therapeutic approaches related to joint health in horses.
Clarke EJ, Johnson E, Caamaño Gutierrez E, Andersen C, Berg LC, Jenkins RE, Lindegaard C, Uvebrant K, Lundgren-Åkerlund E, Turlo A, James V....Equine 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 in...
Müller EMT, Ehrle A, Pozzi A, Lasarzik de Ascurra J, Lischer CJ, Kümmerle JM.To describe open reduction and surgical stabilization of a coxofemoral luxation in a pony using a modified toggle pin technique and prosthetic joint capsule reconstruction without osteotomy of the greater trochanter. Methods: A 2-year-old Shetland pony with a bodyweight of 167 kg. Methods: Case report. Methods: Radiographic examination confirmed craniodorsal luxation of the left coxofemoral joint. An open reduction with the aid of a pulley system was performed. A toggle pin was inserted through a bone tunnel extending from the level of the femoral shaft through the femoral head and the cente...
Wolkowski DD, McCarthy RD, Schoonover MJ, Taylor JD, Eastman TG.Evaluate effects of acellular equine liquid amnion allograft (ELAA) injected into healthy equine joints. Methods: Randomized, blinded, controlled experiment. Methods: Eight healthy adult horses. Methods: One intercarpal joint (ICJ) of each horse was randomly assigned to be injected with 1.5 ml of ELAA (treatment) while the contralateral ICJ was injected with 1.5 ml of 0.9% NaCl (control). Subjective lameness evaluation, force plate analysis, and synovial fluid analysis, including interleukin-1 receptor antagonist (IL-1ra) analysis, were performed before (day 0) and at days 1, 3, 5, and 10. S...
Cassano JM, Marycz K, Horna M, Nogues MP, Morgan JM, Herrmann DB, Galuppo LD, Vapniarsky N.No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood ...
Whisenant KD, Ruggles AJ, Stefanovski D, Woodie JB, Hopper SA, Embertson RM.Haematogenous septic arthritis is a major cause of morbidity and mortality in foals. Previous research has demonstrated a variable prognosis for athletic performance in foals diagnosed with septic arthritis. Objective: To determine the racing prognosis for Thoroughbred foals, 6 months of age or less with single septic joint of presumed haematogenous origin without recognised systemic sepsis or other serious comorbidity compared with a group of maternal sibling controls. Methods: Retrospective cohort study. Methods: Data were collected from Rood and Riddle Equine Hospital in-patient records fro...
Tnibar A.Recent clinical and experimental trials have demonstrated that intra-articular 2.5% Polyacrylamide hydrogel (PAAG) is highly effective (82.5% free of lameness horses at 2 year follow-up), lasting and safe for the treatment of equine osteoarthritis (OA). Over the last decade, intra-articular 2.5% PAAG has shown to be a potent and promising drug in the medication of OA in horses, as no other single medical treatment for OA has such prolonged efficacy. Most of these studies were presenting some limitations. Preliminary observations on the mechanisms of action of intra-articular 2.5% PAAG support ...
Mustonen AM, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkänen A, Paakkonen T, Rilla K, Niemelä T, Nieminen P.Osteoarthritis (OA) is a degenerative joint disease with inadequately understood pathogenesis leading to pain and functional limitations. Extracellular vesicles (EVs) released by synovial joint cells can induce both pro- and anti-OA effects. Hyaluronic acid (HA) lubricates the surfaces of articular cartilage and is one of the bioactive molecules transported by EVs. In humans, altered EV counts and composition can be observed in OA synovial fluid (SF), while EV research is in early stages in the horse-a well-recognized OA model. The aim was to characterize SF EVs and their HA cargo in 19 horses...
Perrier M, Manso-Díaz G, Dunkel B.Trigeminal nerve-mediated head-shaking (TNMH) in horses is a diagnosis made by exclusion. Computed tomography (CT) is frequently used to identify any disease process that could cause the clinical signs of head-shaking. Although abnormalities are frequently identified, it is unknown whether treatment of these conditions improves clinical signs. Objective: To ascertain the clinical significance of CT findings in horses presented with a complaint of head-shaking. Methods: Retrospective case series. Methods: CT and patient records were reviewed and all abnormal findings and any treatments subseque...
Goff L.This article provides the equine practitioner with a review of sacroiliac joint pain and dysfunction and outlines the importance of providing a specific prescription for a safe and effective therapeutic exercise program. The continuum of clinical dysfunction associated with the sacroiliac region is presented with prescribed interventions. The intent is to encourage the practitioner to perform a thorough assessment of the sacroiliac joint and the adjacent soft tissues and to use sound clinical reasoning to formulate a therapeutic exercise plan.
Faulkner J, Vanderperren K, Duchateau L, O'Sullivan C.Ascertain the radiographic prevalence and variation in characteristics of juvenile osteochondral conditions (JOC) in the proximal interphalangeal joint (PIPJ) of Australian Thoroughbred racehorse yearlings. Establish whether there are any significant associations with public auction sale results and racing performance. Unassigned: Retrospective evaluation of 1,098 yearling repository radiograph sets. Comparison of sales results and whole career racing performance of the case group with two control groups: maternal siblings ( = 397) and yearlings without PIP JOC ( = 391). Unassigned: 6.3% of ye...
Vergara-Hernandez FB, Panek CL, Nielsen BD, Robison CI, Colbath AC.To determine the effects of clodronate disodium (CLO) on control and recombinant equine interleukin-1β (IL-1β)-treated equine joint tissues. Methods: In vitro experimental study. Methods: Cartilage explants, chondrocytes, and synoviocytes (n = 3 horses). Methods: Monolayer cultures of chondrocytes and synoviocytes from three horses were subjected to: control media (CON), 5 ng/ml CLO (C/low), 50 ng/ml CLO (C/med), 100 ng/ml CLO (C/high), with and without IL-1β, and 10 ng/ml IL-1β (IL) alone for 72 hours. Cartilage explants from three horses were subjected to CON, IL, C/low, and C/...
Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR.With an intrinsically low ability for self-repair, articular cartilage injuries often progress to cartilage loss and joint degeneration resulting in osteoarthritis (OA). Osteoarthritis and the associated articular cartilage changes can be debilitating, resulting in lameness and functional disability both in human and equine patients. While articular cartilage damage plays a central role in the pathogenesis of OA, the contribution of other joint tissues to the pathogenesis of OA has increasingly been recognized thus prompting a whole organ approach for therapeutic strategies. Gene therapy metho...
Hall NP, Heaton KT, Farnsworth KD, Ragle CA.This report evaluates the use of 4.5- and 5.5-mm cannulated drill bits for articular cartilage removal from the proximal interphalangeal joints of equine cadaver limbs. Limbs from 8 equine cadavers, all with normal proximal interphalangeal joints. Proximal interphalangeal joints of 32 limbs from 8 equine cadavers were drilled using either 4.5- or 5.5-mm cannulated drill bits. Pastern joints were then disarticulated, and intra-articular drilling was evaluated by visual inspection. Post-drilling evaluation revealed complete intra-articular drilling occurred in all 32 joints. Canulated 4.5- and 5...
Guerri G, Palozzo A, Straticò P, Varasano V, Celani G, Di Francesco P, Vignoli M, Petrizzi L.(1) Two-dimensional shear wave elastography (2D-SWE) employs an ultrasound impulse to produce transversely oriented shear waves, which travel through the surrounding tissue according to the stiffness of the tissue itself. The study aimed to assess the reliability of 2D-SWE for evaluating the elastosonographic appearance of the distal attachment of the fetlock joint capsule (DJC) in sound horses and in horses with osteoarthritis (OA) (2). According to a thorough evaluation of metacarpophalangeal joint (MCPJ), adult horses were divided in a sound Group (H) and in OA Group (P). Thereafter, a 2D-S...
Hayden LR, Stoker AM, Johnson PJ, McCracken MJ.To determine the following: (1) whether an irrigation solution that is hyperosmolar (HYPER) relative to synovial fluid decreases tissue extravasation during an arthroscopic protocol when compared to a relatively hypoosmolar solution, (2) the safety of a HYPER solution based on viability of joint tissues following joint irrigation, and (3) if the use of a HYPER solution decreases water content in stifle joint tissue. Methods: 8 adult horses. Methods: A prospective, blinded, randomized controlled trial was performed to compare lactated Ringer's solution (LRS; 273 mOsm/L) and a HYPER (600 mOsm/L)...
Hernandez SM, Begum L, Keller LE, Fu Q, Zhang S, Fortier LA.To identify chondroprotective factors as potential disease-modifying osteoarthritis treatments using an unbiased, bottom-up proteomics approach. Methods: Paired equine cartilage explants and synovial membrane were collected postmortem from 4 horses with no history of lameness and grossly normal joints at necropsy. Methods: Six groups were established: cartilage, synoviocytes, and cartilage + synoviocytes (coculture), all with or without interleukin (IL)-1β. The catabolic effect of IL-1β was verified by glycosaminoglycan (GAG) released from cartilage into media by 1,9-dimethyl-methylene blue ...
McParland TJ, Horne CR, Robertson JB, Schnabel LV, Nelson NC.Limited information exists regarding associations between distal interphalangeal joint (DIPJ) abnormalities and synovial invagination changes in the distal sesamoid (navicular) bone. This retrospective, analytical study aimed to measure specific characteristics of the synovial invaginations of the navicular bone to determine whether any single characteristic was associated with abnormalities in the DIPJ or navicular apparatus (NA) using high field MRI and a sample of 200 horses' feet. The DIPJ and NA were graded independently by three scorers. The grades were averaged, creating a global pathol...
Miagkoff L, Girard CA, St-Jean G, Richard H, Beauchamp G, Laverty S.Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid (CB) receptors are now considered to be promising therapeutic targets in human rheumatology for pain and inflammation, however, little is known about the equine endocannabinoid system. Objective: The primary goal was to assess the presence and expression pattern of CB1 and CB2 in the synovium of healthy joints. A secondary goal was to explore the relationship between the CB expression, degree of synovitis and OA pathology. Methods: Ex vivo experimental study. Methods: Metacarpophalangeal joints (n = 25) from a tissue bank w...
Jain S, Patil SG, Chinta G, Alluri KV.Lameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti-inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio. We conducted a 12-week single-center, randomized, blinded, placebo-controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2-4 on the American Association of Equine Practitioners (AAEP) scale. Twenty-two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or place...
Boger BL, Manfredi JM, Yob C, Weber PSD, Jacobs CC.Diagnosis of equine septic arthritis is not straightforward, and increasing time between onset, diagnosis, and treatment can have serious consequences for quality of life. Defensins are used in diagnosis of human joint infection. The presence of beta defensins (BDs) in equine synovial fluid and their utility as a biomarker of sepsis has not been investigated; therefore, our objectives were to (1) compare in vitro gene expression of lipopolysaccharide (LPS)-stimulated equine neutrophils to unstimulated neutrophils and (2) compare BD protein expression from normal, aseptically inflamed, and sept...
Ramos S, Pinto A, Crespo J, Marques JP, Bettencourt E, Gama LT, Monteiro S.Osteochondrosis (osteochondritis dissecans), OC(D), is an important joint disorder that has been studied through the years in different breeds but, to our knowledge, there are no reports of its prevalence in Lusitano horses. The aim of this study was to assess the prevalence of OC(D) in Lusitanos, define the characteristics of the disorder in this breed and compare with Spanish Purebred horses. This is a retrospective study that analysed the radiographs from the metacarpometatarsophalangeal, tarsocrural and femoropatellar joints that were taken in 302 Lusitano horses (1-12 years; obtained from...
Andersen C, Jacobsen S, Walters M, Lindegaard C.Osteoarthritis (OA) is a significant health issue in humans as well as horses. Experimental models of equine carpal OA have been used to investigate OA pathogenesis and potential therapeutic candidates. A 5-scale scoring system (OARSI) for macroscopic pathological cartilage changes already exists, but there is a need for a scoring system with better differentiation of severity. The aim of this study was therefore to develop and validate such a scoring system. Results: New scoring system were developed for cartilage erosions (Copenhagen Equine Total Cartilage Score, CEqTCS) along with synovial ...
Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ.Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimul...
Goodwin M, Klufts M, Workman J, Thambyah A, Vanholsbeeck F.To explore the ability of polarisation-sensitive optical coherence tomography (PS-OCT) to rapidly identify subtle signs of tissue degeneration in the equine joint. Polarisation-sensitive optical coherence tomography (PS-OCT) images were systematically acquired in four locations along the medial and lateral condyles of the third metacarpal bone in five dissected equine specimens. Intensity and retardation PS-OCT images, and anomalies observed therein, were then compared and validated with high resolution images of the tissue sections obtained using Differential Interference contrast (DIC) optic...
Yamada ALM, do Prado Vendruscolo C, Marsiglia MF, Sotelo EDP, Agreste FR, Seidel SRT, Fülber J, Baccarin RYA, da Silva LCLC.Combined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound base...
Seabaugh KA, Barrett MF, Rao S, McIlwraith CW, Frisbie DD.Osteoarthritis (OA) is a common problem in horses. Several oral supplements have been proposed as treatments for horses with OA. The object of this study was to evaluate the use of the oil extract from the seeds of (BO) for the treatment of experimentally induced OA in horses. OA was induced in 16, 2-5 year old horses in one middle carpal joint on Day 0; the other limb underwent a sham operation. Once daily oral treatment with BO or placebo was initiated on Day 0 and continued to Day 70. All horses were exercised 5 days a week starting on Day 14 through Day 70. The horses were evaluated every...
Gilbertie JM, Schaer TP, Engiles JB, Seiler GS, Deddens BL, Schubert AG, Jacob ME, Stefanovski D, Ruthel G, Hickok NJ, Stowe DM, Frink A, Schnabel LV.The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro st...
Logan AA, Nielsen BD, Hiney KM, Robison CI, Manfredi JM, Buskirk DD, Popovich JM.Circular exercise is used in many equestrian disciplines and this study aimed to determine if circle diameter impacts juvenile animal forelimb bone and joint health. On day 0, 24 calves at 9 weeks of age were assigned the following exercise treatments: small circle (12 m clockwise), large circle (18-m clockwise), treadmill, or non-exercised control. Exercise was initiated at 1.1−1.5 m/s for 5 min/d and increased 5 min weekly until reaching 30 min/d. On day 49, synovial fluid was collected from multiple joints, cartilage was collected from the proximal surface of fused third and fourth metaca...
Soroko M, Górniak W, Godlewska M, Howell K.The aim of this study was to evaluate the influence of training on body surface temperature over the joints in racehorses, measured by infrared thermography. The study involved monitoring of 14 Thoroughbred racehorses in 6 imaging sessions over a period of 3 months. Temperature measurements of the forelimb and hindlimb joints were made before and just after training. Joint temperature of limbs increased significantly after training. Environmental temperature had a statistically significant influence on surface temperature over the joints. The lowest surface temperatures were recorded over the ...
Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N, François I, Lechartier A, Aebischer D, Moncelet AS, Maddens S.The purpose of this prospective study was to evaluate the effects of single and repeated intra-articular administration of allogeneic, umbilical cord-derived, neonatal mesenchymal stem cells (MSC) in horses with lameness due to osteoarthritis (OA) of a metacarpophalangeal joint (MPJ). Twenty-eight horses were included. Horses were divided into two groups. Horses in group MSC1 received an MSC injection at M0 and a placebo injection at M1 (1 month after M0). Horses in group MSC2 received MSC injections at M0 and at M1. Joint injections were performed with a blinded syringe. Clinical assessment w...
McIlwraith CW, Kawcak CE, Frisbie DD, Little CB, Clegg PD, Peffers MJ, Karsdal MA, Ekman S, Laverty S, Slayden RA, Sandell LJ, Lohmander LS, Kraus VB.We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to...
Lacitignola L, Fanizzi FP, Francioso E, Crovace A.Proton magnetic resonance spectroscopy (1H NMR) has been successfully used in the study of many biological fluids. The data presented here report on the metabolic profiles of normal equine synovial fluids compared with osteoarthritic (OA) fluids. Twenty-five OA synovial fluid samples and eight normal ones were collected from the forelimb fetlock joint in 22 horses, aged between five and 24 years. 1H NMR spectroscopy was carried out with a Bruker Avance DRX 500 equiped with a cryo-magnet working at 11 Tesla, and 'Mestre-C 4.9.9.6' software was used to analyze the spectra. The study assessed the...
Muir P, McCarthy J, Radtke CL, Markel MD, Santschi EM, Scollay MC, Kalscheur VL.The mechanisms that regulate functional adaptation of the articular ends of long bones are poorly understood. However, endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate and epiphyseal trabeculae are important components of the adaptive response. We performed a histologic study of the distal end of the third metacarpal/metatarsal bone of Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified sections were prepared. The Thoroughbred racehorse is a model of an extreme athlete which experiences particularly high cyclic strains in ...
Jacobsen S, Thomsen MH, Nanni S.To determine serum amyloid A (SAA) concentrations in serum and synovial fluid from healthy horses and horses with joint disease and assess the effect of repeated arthrocentesis on SAA concentrations in synovial fluid. Animals-10 healthy horses and 21 horses with various types of joint disease. Methods: Serum and synovial fluid samples were obtained from each horse. In 5 of the 10 healthy horses, arthrocentesis was repeated 9 times. Concentrations of SAA were determined via immunoturbidometry. Results: Serum and synovial fluid SAA concentrations were less than the assay detection limit in healt...
Frisbie DD, Kawcak CE, Trotter GW, Powers BE, Walton RM, McIlwraith CW.The objective of this study was to determine the effects of intra-articularly administered triamcinolone acetonide (TA) in exercised equine athletes with carpal osteochondral fragmentation. Eighteen horses were randomly assigned to each of 3 groups. An osteochondral chip fragment was created in one randomly chosen intercarpal joint of each horse. Both intercarpal joints in the placebo control group (CNT) horses were injected with intra-articular administration (IA) of polyionic fluid. Both joints in the TA control group (TA CNT) horses were treated with 12 mg of TA in the intercarpal joint wit...
de Grauw JC, van de Lest CH, van Weeren PR.Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation. Methods: Localized inflammation was induced in the intercarpal joi...
Kawcak CE, McIlwraith CW, Norrdin RW, Park RD, James SP.Subchondral bone plays a role in the pathogenesis of osteochondral damage and osteoarthritis in horses and humans. Osteochondral fragmentation and fracture, subchondral bone necrosis and osteoarthritis are common diseases in athletic horses, and subchondral bone is now thought to play an integral role in the pathogenesis of these diseases. There have been numerous research efforts focused on articular cartilage damage and its pathogenesis, yet comparatively little effort focused on subchondral bone pathology or the coordinated disease states of the osteochondral tissues. The purpose of this re...
Laverty S, Sandy JD, Celeste C, Vachon P, Marier JF, Plaas AH.To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels. Methods: Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dos...
Park J, Sutradhar BC, Hong G, Choi SH, Kim G.To compare the chondrotoxicity of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes in vitro. Methods: Prospective, experimental study. Methods: Equine articular chondrocytes. Methods: Primary cultured equine chondrocytes were exposed to 0.5% bupivacaine, 2% lidocaine, or 2% mepivacaine for 30 or 60 minutes. After treatment, cell viability was evaluated by trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay in a dose dependent manner. Apoptosis and necrosis of chondrocytes were analyzed with the double stain...
Steinbusch MM, Fang Y, Milner PI, Clegg PD, Young DA, Welting TJ, Peffers MJ.The development of effective treatments for the age-related disease osteoarthritis and the ability to predict disease progression has been hampered by the lack of biomarkers able to demonstrate the course of the disease. Profiling the expression patterns of small nucleolar RNAs (snoRNAs) in joint ageing and OA may provide diagnostic biomarkers and therapeutic targets. This study determined expression patterns of snoRNAs in joint ageing and OA and examined them as potential biomarkers. Using SnoRNASeq and real-time quantitative PCR (qRT-PCR) we demonstrate snoRNA expression levels in murine age...
Bertuglia A, Pagliara E, Grego E, Ricci A, Brkljaca-Bottegaro N.Joint 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 disea...
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...
Textor JA, Willits NH, Tablin F.Platelet-rich plasma (PRP) products may be useful for treatment of joint disease in horses, but may contain undesirable pro-inflammatory cytokines in addition to growth factors. This study investigated whether autologous PRP increases synovial fluid growth factor and cytokine concentrations when injected into normal equine metacarpophalangeal and metatarsophalangeal (fetlock) joints. Fetlock joints of seven healthy horses received one of four treatments: saline, resting PRP, CaCl2-activated PRP or thrombin-activated PRP. Synovial fluid was sampled prior to injection and at 6, 24, 48 and 96 h p...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Ribera T, Monreal L, Armengou L, Ríos J, Prades M.Increased synovial fibrinolytic activity (detected by increases in synovial D-Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. Objective: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D-Dimer concentrations. Methods: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Methods: Prospective obs...
Palmer JL, Bertone AL.The use of extremely small dosages of intra-articular E. coli lipopolysaccharide (LPS) endotoxin can create a model of synovitis that mimics acute synovitis in horses. Dosages of 5000 ng, 25 ng, 0.5 ng, 0.25 ng, 0.17 ng and 0.125 ng per joint were injected into various joints of a total of 6 horses. The dose response of LPS on clinical signs and synovial fluid parameters was evaluated at baseline and 12, 24, 36 and 48 h after LPS injection. Peripheral venous blood analysis was performed at baseline and at 0, 4, and 12 h after LPS injection. Dosages greater than 0.5 ng/joint resulted in clinica...
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...
Penell JC, Egenvall A, Bonnett BN, Olson P, Pringle J.The principal aim of this study was to analyse the incidence of disease due to general and more specific causes among over 100,000 horses covered by complete insurance for veterinary care by a Swedish insurance company during 1997 to 2000. The database was used to calculate the rate of cause-specific morbidity in horses of different ages, sexes and breed groups kept in different regions with different human population densities. The joints were the most commonly affected part of the body, followed by unspecified/whole body, the skin and the digestive system. The most common specific diagnosis ...
Peffers MJ, McDermott B, Clegg PD, Riggs CM.The aim of the study was to characterise the protein complement of synovial fluid (SF) in health and osteoarthritis (OA) using liquid chromatography mass spectrometry (LC-MS/MS) following peptide-based depletion of high abundance proteins. Methods: SF was used from nine normal and nine OA Thoroughbred horses. Samples were analysed with LC-MS/MS using a NanoAcquity™ LC coupled to an LTQ Orbitrap Velos. In order to enrich the lower-abundance protein fractions protein equalisation was first undertaken using ProteoMiner™. Progenesis-QI™ LC-MS software was used for label-free quantification. ...
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...
Céleste C, Ionescu M, Robin Poole A, Laverty S.Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis w...
Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ.Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2,...
Vandeweerd JM, Coisnon C, Clegg P, Cambier C, Pierson A, Hontoir F, Saegerman C, Gustin P, Buczinski S.Various treatments of osteoarthritis (OA) have been described, including use of nutraceuticals. Objective: To review systematically the literature about the effects of nutraceuticals on clinical signs of pain or abnormal locomotion in horses, dogs, and cats, and to discuss methodological aspects of trials and systematic reviews. Methods: A systematic search of controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs, and cats was performed, using Medline, CAB Abstracts, and Google Scholar. Scientific evidence was evaluated by means of criteria proposed by the Food and Dr...
Boere J, Malda J, van de Lest CHA, van Weeren PR, Wauben MHM.The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and th...
Donnell JR, Frisbie DD, King MR, Goodrich LR, Haussler KK.When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by e...
van Loon JP, de Grauw JC, van Dierendonck M, L'ami JJ, Back W, van Weeren PR.Intra-articular administration of morphine as a local analgesic and anti-inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti-inflammatory efficacy. Objective: To use an inflammatory orthopaedic pain model to investigate the analgesic and anti-inflammatory effects of intra-articularly administered morphine as a new treatment modality in horses with acute arthritis. Methods: In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra-articular injection of 0.5 ng lipopolyssacharide (LP...
Soroko M, Howell K, Dudek K.The aim of the study was to describe the dependence on ambient temperature of distal joint temperature at the forelimbs of racehorses. The study also investigated the influence of differing ambient temperatures on the temperature difference between joints: this was measured ipsilaterally (i.e. between the carpal and fetlock joints along each forelimb) and contralaterally (i.e. between the same joints of the left and right forelimbs). Sixty-four healthy racehorses were monitored over 10 months. At each session, three thermographic images were taken of the dorsal, lateral and medial aspects of t...
Reesink HL, Watts AE, Mohammed HO, Jay GD, Nixon AJ.The goals of this study were (1) to quantify proteoglycan 4 (PRG4) gene expression; (2) to assess lubricin immunostaining; and (3) to measure synovial fluid lubricin concentrations in clinical and experimental models of equine carpal osteoarthritis (OA). Lubricin synovial fluid concentrations and cartilage and synovial membrane PRG4 expression were analyzed in research horses undergoing experimental OA induction (n = 8) and in equine clinical patients with carpal OA (n = 58). Lubricin concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay, and PRG4 expressio...
