Osteoarthritis (OA) in horses is a degenerative joint disease characterized by the progressive deterioration of articular cartilage, subchondral bone changes, and synovial inflammation. This condition can result in pain, reduced mobility, and impaired performance in affected animals. Osteoarthritis is commonly observed in athletic horses due to repetitive joint stress, but it can also occur in older horses as part of the natural aging process. Diagnosis typically involves clinical examination, imaging techniques such as radiography or MRI, and sometimes synovial fluid analysis. Management strategies focus on alleviating pain, reducing inflammation, and slowing disease progression through pharmacological treatments, physical therapy, and sometimes surgical interventions. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, and management of osteoarthritis in equine patients.
Herbst AC, Coleman MC, Macon EL, Harris PA, Adams AA.Information on health care and health status of U.S. senior horses (≥15 years of age) is currently sparse. Objective: (A) Provide an overview of owner-reported (1) medical conditions, (2) management/treatment practices for equine metabolic syndrome and pituitary pars intermedia dysfunction (PPID), (3) frequencies of routine health care practices and (4) supplement and pharmaceutical use in U.S. senior horses (≥15 years of age). (B) Evaluate potential risk factors for certain medical conditions and for low routine health care. Methods: Online survey. Methods: Descriptive and inferential...
Usimaki A, Ciamillo SA, Barot D, Linardi RL, Engiles JB, Ortved KF.Autologous protein solution (APS) has been shown to decrease lameness in horses with osteoarthritis (OA). Synovitis is an early driver of OA, providing an opportunity to intervene in the progression of disease via intra-articular (IA) therapeutics. Objective: The objective of this study was to investigate the effects of a single IA APS injection in horses with interleukin-1β (IL-1β)-induced synovitis. We hypothesised that APS would decrease joint swelling and lameness, improve synovial fluid parameters and improve joint pathology scores in horses compared with untreated controls. Methods: Ra...
Kushida C, Tamura N, Kasashima Y, Sato K, Arai K.In equine regenerative medicine using bone marrow-derived mesenchymal stem/stromal cells (BM-MSC), the importance of the quality management of BM-MSC has been widely recognized. However, there is little information concerning the relationship between cellular senescence and the stemness in equine BM-MSC. In this study, we showed that stemness markers (NANOG, OCT4, SOX2 and telomerase reverse transcriptase) and colony forming unit-fibroblast apparently decreased accompanied with incidence of senescence-associated β-galactosidase-positive cells by repeated passage. Additionally, we suggested th...
Pereira LO, DE Souza AF, Spagnolo JD, Yamada ALM, Salgado DMRA, DE Zoppa ALDV.Osteoarthritis (OA) is a prevalent condition in horses, leading to changes in trabecular bone structure and radiographic texture. Although fractal dimension (FD) and lacunarity have been applied to quantify these changes in humans, their application in horses remains nascent. This study evaluated the use of FD, bone area fraction (BA/TA), and lacunarity in quantifying trabecular bone differences in the proximal phalanx (P1) in 50 radiographic examinations of equine metacarpophalangeal joints with varying OA degrees. In the dorsopalmar view, regions of interest were defined in the trabecular bo...
Vishwanath K, McClure SR, Bonassar LJ.Intra-articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively lubricate and bind to the surface of cartilage in vitro. However, its ability to localize to cartilage and alter the tribological properties of the tissue in a live articulating large animal joint is not known. The goal of this study was to...
Stucki G, Fürst AE, Jackson MA.The aim of this retrospective study is to describe and compare conservative and surgical treatment of navicular fractures in horses. An attempt is made to identify critical points that can favorably influence the prognosis of this orthopedic disease. All horses treated for a navicular fracture at the Equine Clinic, Vetsuisse Faculty, University of Zurich between 2005 and 2017 were included in this study. The severity of lameness at initial examination, radiographic assessment, hoof conformation, treatment (conservative or surgical), complications and outcome were determined from the medical re...
Nagy A, Dyson S.There is a limited description of magnetic resonance imaging (MRI) and no information on computed tomographic (CT) findings in the fetlock of non-lame, non-racing sports horses. This study aimed to document comparative CT, MRI and radiographic findings in the metacarpophalangeal joints of showjumpers in full work. Clinical and gait assessments, low-field MRI, fan-beam CT and radiographic examinations of both metacarpophalangeal joints were performed on 31 showjumpers. Images were analysed descriptively. In most limbs (53/62, 85.5%), there were CT and MRI changes consistent with densification i...
Ducrocq M, Kamus L, Richard H, Beauchamp G, Janvier V, Laverty S.Stifle osteoarthritis (OA) lesions are most common in the medial femorotibial (MFT) compartment. Their characterisation and mapping will inform equine veterinarians towards an accurate diagnosis of OA. Objective: Investigate and map micro-CT (μCT) changes in the hyaline articular cartilage (HAC) in the medial femoral condyle (MFC) and medial tibial plateau (MTP). Methods: Ex vivo cadaveric. Methods: Stifles (n = 7 OA and 17 control [CO]) were retrieved from a tissue bank. The MFC and MFT were imaged with μCT. Regions of interest (ROIs) were cranial (MFCcr; MTPcr) and caudal (MFCca; MTPca...
Reis IL, Lopes B, Sousa P, Sousa AC, Caseiro AR, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC.Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managin...
Goodrich LR, McIlwraith CW, Grieger J, Kraus VB, Stabler T, Werpy N, Phillips J, Samulski RJ, Frisbie D.To evaluate the effects of a gene transfer approach to IL-1β inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. Methods: 16 horses were utilized for the study. Methods: All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra o...
Connard SS, Gaesser AM, Clarke EJ, Linardi RL, Even KM, Engiles JB, Koch DW, Peffers MJ, Ortved KF.The objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring post-traumatic osteoarthritis (PTOA). Methods: EVs were isolated from plasma and synovial fluid from horses with (n = 6) and without (n = 6) PTOA. Methods: Plasma and synovial fluid EVs were characterized with respect to quantity, size, and surface markers. Small RNA sequencing was performed, and differentially expressed microRNAs (miRNAs) underwent bioinformatic analysis to identify putative targets and to explore potential associa...
Gaesser AM, Usimaki AIJ, Barot DA, Linardi RL, Molugu S, Musante L, Ortved KF.Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have emerged as a biotherapeutic for osteoarthritis; however, manufacturing large quantities is not practical using traditional monolayer (2-D) culture. We aimed to examine the effects of 3-D and 2-D culture 2 types of media: Dulbecco modified Eagle medium and a commercially available medium (CM) on EV yield. Methods: Banked bone marrow-derived MSCs (BM-MSCs) from 6 healthy, young horses were used. Methods: 4 microcarriers (collagen-coated polystyrene, uncoated polystyrene, collagen-coated dextran, and uncoated dextran) were tested in st...
Andersen C, Walters M, Bundgaard L, Berg LC, Vonk LA, Lundgren-Åkerlund E, Henriksen BL, Lindegaard C, Skovgaard K, Jacobsen S.Osteoarthritis (OA) remains a major cause of lameness in horses, which leads to lost days of training and early retirement. Still, the underlying pathological processes are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that serve as regulators of many biological processes including OA. Analysis of miRNA expression in diseased joint tissues such as cartilage and synovial membrane may help to elucidate OA pathology. Since integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) have shown mitigating effect on equine OA we here investigated the effect of integrin α10...
McClure SR, Peitzmeier MD, Jackman BR, Evans RB, Ziegler CL, Ganta CK.Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. Methods: 8 healthy horses. Methods: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% ...
Panizzi L, Vignes M, Dittmer KE, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Riley CB.Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction...
Jasiński T, Turek B, Kaczorowski M, Brehm W, Skierbiszewska K, Bonecka J, Domino M.Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and ...
Antunes J, Salcedo-Jiménez R, Lively S, Potla P, Coté N, Dubois MS, Koenig J, Kapoor M, LaMarre J, Koch TG.Osteoarthritis (OA) is a leading cause of lameness in horses with no effective disease-modifying treatment and challenging early diagnosis. OA is considered a disease of the joint involving the articular cartilage, subchondral bone, synovial membrane, and ligaments. Osteochondritis dissecans (OCD) is a joint disease consisting of focal defects in the osteochondral unit which may progress to OA later in life. MicroRNAs (miRNAs) have been recognized as small non-coding RNAs that regulate a variety of biological processes and have been detected in biological fluids. MiRNAs are currently investiga...
Domańska-Kruppa N, Wierzbicka M, Stefanik E.Back pain is common in ridden horses. Back diseases in horses include Impinging Dorsal Spinous Processes, Ventral Spondylosis, Osteoarthritis of Articular Process, Intervertebral Discs Disease, Vertebral Fractures, Conformational Abnormalities, Desmopathy of the Supraspinous Ligament, Desmopathy of the Intraspinous Ligament, and Longissimus Muscle Strain. Back pain may also develop as a result of lameness (particularly hindlimb lameness). A poorly fitting saddle and an unbalanced rider are also considered important factors influencing the development of back pain in horses. The conventional di...
Ortved KF, Alward L, Cowles B, Linardi R, Barot D, Usimaki A, Fedie JR, Amodie D, Goodrich LR.Alpha 2 macroglobulin (A2M), a multi-functional protein in the plasma protease inhibitor class, regulates proinflammatory cytokines and the clearance of chondrodestructive enzymes in cases of joint injury and osteoarthritis (OA). The purpose of this study was to compare A2M concentrations in equine plasma samples processed by three commercial devices developed for stall-side regenerative joint therapy. Unassigned: Plasma samples were obtained from healthy adult horses ( = 13). Mass spectrometry analysis was used to determine the concentration of protein analytes in each sample. Selected re...
Interlandi C, Tabbì M, Di Pietro S, D'Angelo F, Costa GL, Arfuso F, Giudice E, Licata P, Macrì D, Crupi R, Gugliandolo E.The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain...
Kang M, Lee S, Seo JP, Lee EB, Ahn D, Shin J, Paik YK, Jo D.The use of the FDA-approved osteoinductive growth factor BMP2 is widespread for bone regeneration. However, its clinical application has been hindered by limitations in cell permeability and a short half-life in circulation. To address this issue, we have developed a modified version of BMP2, referred to as Cell Permeable (CP)-BMP2, which possesses improved cell permeability. CP-BMP2 incorporates an advanced macromolecular transduction domain (aMTD) to facilitate transfer across the plasma membrane, a solubilization domain, and recombinant human BMP2. Compared to traditional rhBMP2, CP-BMP2 ex...
Clarke E, Varela L, Jenkins RE, Lozano-Andrés E, Cywińska A, Przewozny M, van Weeren PR, van de Lest CHA, Peffers M, Wauben MHM.Osteoarthritis causes progressive joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Currently, osteoarthritis is diagnosed at late stages through clinical examination and radiographic imaging, hence it is challenging to address and provide timely therapeutic interventions to slow disease progression or ameliorate symptoms. Extracellular vesicles are cell-derived vesicles that play a key role in cell-to-cell communication and are potential sources for specific composite biomarker panel discovery. We here used a multi-omics strategy combining proteomics and p...
Peng C, Yang L, Labens R, Gao Y, Zhu Y, Li J.Equine joint disease including septic arthritis (SA) and osteoarthritis (OA) is a critical cause of equine lameness. Platelet-rich plasma (PRP) is one of the most popular regenerative therapies to treat equine OA, even SA, but the evidence in support of the treatment is conflicting. Objective: The aim of the study was to systematically review the current evidence on PRP products used for SA and OA, as well as the efficacy of PRP products as treatment for OA on the basis of a meta-analysis of the available literature. Methods: Systematic review and meta-analysis. Methods: A systematic search of...
Sauer FJ, Hellige M, Beineke A, Geburek F.Few case reports describe equine coxofemoral joint osteoarthritis (CFJOA). Objective: To evaluate diagnostic findings and outcome of horses with CFJOA and to provide a score facilitating radiographic assessment. Methods: Retrospective case series. Methods: History, clinical signs, ultrasonographic, radiographic and intra-articular anaesthesia findings, treatments, outcome, and necropsy results of horses with CFJOA presented between 2002 and 2023 were collated. Radiographic findings were categorised to develop a radiographic score which was applied by two masked examiners. Intra- and inter-obse...
Howard DL, Lancaster B, de Grauw J.An owner-completed questionnaire was designed to monitor the level of chronic pain and impact on quality of life in horses with osteoarthritis (OA). A standardized approach to develop and validate subjective-state scales for clinical use was followed. Scale items were generated through literature review, focus group meetings, and expert panel evaluation. The draft tool was tested for reading level and language ambiguity and piloted in 25 owners/caregivers of horses with osteoarthritis, with factor analysis performed on responses. The resulting revised questionnaire is currently undergoing vali...
Spoormakers TJP, Veraa S, Graat EAM, van Weeren PR, Brommer H.Data on equine lumbar pathology hardly exist in breeds other than Thoroughbreds. Objective: To describe pathological changes of the osseous lumbar vertebral column in Warmblood horses, Shetland ponies and Konik horses. Methods: Descriptive post-mortem study. Methods: The lumbar vertebral columns of 34 Warmblood horses, 28 Shetland ponies, and 18 Konik horses were examined by computed tomography (CT). Osteoarthritis (OA) of articular processes (APJs), OA of intertransverse joints (ITJs), intervertebral disc (IVD) mineralisation, impingement of spinous (SPs) and transverse (TPs) processes and sp...
Della Tommasa S, Brehm W, Farì G, Bernetti A, Imperante A.The utilization of Autologous Conditioned Serum (ACS) for treating osteoarthritis (OA) in horses has seen a notable increase in recent years. In vitro studies have consistently identified ACS as a promising therapy for OA joints, contributing to its growing popularity in OA treatment. Despite this, there is a noticeable absence of systematic reviews focused solely on the clinical data of OA patients treated with ACS, excluding the in vitro perspective. This study aims to address this gap by systematically reviewing the latest literature, concentrating solely on clinical data in in vivo studies...
Rouge M, Legendre F, Elkhatib R, Delalande C, Cognié J, Reigner F, Barrière P, Deleuze S, Hanoux V, Galéra P, Bouraïma-Lelong H.The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE...
Andersen C, Jacobsen S, Uvebrant K, Griffin JF, Vonk LA, Walters M, Berg LC, Lundgren-Åkerlund E, Lindegaard C.Integrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) and in animal models . The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs. Methods: OA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 10 integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carp...
Morgan RE, Fiske-Jackson A, Chang YM.Osteoarthritis of the equine thoracolumbar articular process joints (APJs) has been linked to back pain. Changes are commonly diagnosed through nuclear scintigraphy, radiography and ultrasonography (US). Objective: (1) To assess the agreement of APJ grades between US and computed tomography (CT) images; (2) to assess the effect of location on the agreement of APJ grades between US and CT images. It was hypothesised that: (1) Periarticular modelling and modification of the joint space would have the highest and lowest agreement between US and CT images, respectively; (2) Caudal thoracolumbar AP...
Wang Y, Chen Y, Wei Y.Clinical therapeutics for the regeneration of osteochondral defects (OCD) in the early stages of osteoarthritis remain an enormous challenge in orthopaedics. For in-depth studies of tissue engineering and regenerative medicine in terms of OCD treatment, the utility of an optimal OCD animal model is crucial for assessing the effects of implanted biomaterials on the repair of damaged osteochondral tissues. Currently, the most frequently used in vivo animal models for OCD regeneration include mice, rats, rabbits, dogs, pigs, goats, sheep, horses and nonhuman primates. However, there is no single ...
van Weeren PR, Back W.Musculoskeletal disorders are the most prevalent health problem in aging horses. They are not life threatening, but are painful and an important welfare issue. Chronic joint disease (osteoarthritis) and chronic laminitis are the most prevalent. Treating osteoarthritis in the elderly horse is similar to treating performance horses, but aims at providing a stable situation with optimal comfort. Immediate medical treatment of flare-ups, long-term pain management, and adaptation of exercise and living conditions are the mainstays of treatment. Laminitis in the geriatric horse is related often to p...
Evans CH, Chevalier X, Wehling P.Autologous conditioned serum was developed in the mid 1990s as an expeditious, practical, and relatively inexpensive means of generating the interleukin-1 receptor antagonist, a naturally occurring inhibitor of the cytokine interleukin-1. The latter is thought to be an important mediator of inflammation, pain, and tissue destruction in musculoskeletal conditions. ACS has been widely and successfully used in the local treatment of human and equine osteoarthritis and radicular compression; it has also shown promise in treating tendinopathies, muscle injuries, and tunnel widening after reconstruc...
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...
Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S, Oustric D, Jung M, Lepage O, Steinberg R, Jorgensen C, Noel D.Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. Methods: ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluat...
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...
Barrachina L, Cequier A, Romero A, Vitoria A, Zaragoza P, Vázquez FJ, Rodellar C.Antibody production after allogeneic administration of mesenchymal stem cells (MSCs) could impact their clinical application. Proinflammatory priming of MSCs can potentiate their regulatory ability in vivo but increased expression of major histocompatibility complex (MHC) might augment their immunogenicity, potentially leading to immune memory thus limiting repeated allogeneic administration. This study aimed at evaluating the production of cytotoxic allo-antibodies directed against donor's ELA (equine leukocyte antigen) in mismatched and halfmatched horses receiving repeated intraarticular ad...
Frisbie DD, Kawcak CE, McIlwraith CW.OBJECTIVE-To assess the clinical, biochemical, and histologic effects of extracorporeal shock wave therapy (ESWT) in the treatment of horses with experimentally induced osteoarthritis (OA). ANIMALS-Twenty-four 2- to 3-year-old horses without evidence of lameness. PROCEDURES-OA was induced arthroscopically in 1 middle carpal joint of each horse. Fourteen days after induction of OA, horses were treated with a sham ESWT probe (placebo; n = 8), polysulfated glycosaminoglycan (PSGAG) administered IM every 4 days for 28 days as a positive control treatment (8), or ESWT administered on days 14 and 28...
Dias IR, Viegas CA, Carvalho PP.Namely, in the last two decades, large animal models - small ruminants (sheep and goats), pigs, dogs and horses - have been used to study the physiopathology and to develop new therapeutic procedures to treat human clinical osteoarthritis. For that purpose, cartilage and/or osteochondral defects are generally performed in the stifle joint of selected large animal models at the condylar and trochlear femoral areas where spontaneous regeneration should be excluded. Experimental animal care and protection legislation and guideline documents of the US Food and Drug Administration, the American S...
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 ...
Ireland JL, Wylie CE, Collins SN, Verheyen KL, Newton JR.This study aimed to describe the provision of preventive health care and owner-reported disease prevalence in horses and ponies within Great Britain (GB), and to assess geographical variations in health care provision. A cross-sectional survey was conducted, using a postal questionnaire administered to a random sample of veterinary-registered owners of horses and ponies in GB (n=797). The majority of animals received regular preventive health care: 95.6% had regular hoof care; 71.3% were vaccinated for both influenza and tetanus and median time since last anthelmintic administration was 8.7 we...
Goodrich LR, Phillips JN, McIlwraith CW, Foti SB, Grieger JC, Gray SJ, Samulski RJ.Osteoarthritis (OA) affects over 40 million people annually. We evaluated interleukin-1 receptor antagonist (IL-1ra) gene transfer in an equine model based on IL-1ra protein therapy which inhibits inflammation through blocking IL-1. Using the self-complementary adeno-associated virus (scAAV)IL-1ra equine gene as a starting construct, we optimized the transgene cassette by analyzing promoters (cytomegalovirus (CMV) versus chicken β-actin hybrid (CBh)), coding sequences (optimized versus unoptimized), vector capsid (serotype 2 versus chimeric capsid), and biological activity in vitro. AAV serot...
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...
Gale AL, Linardi RL, McClung G, Mammone RM, Ortved KF.Focal cartilage injury occurs commonly and often precipitates OA. Mesenchymal stem cells (MSCs) may be useful for repairing cartilage lesions, thereby preventing joint degeneration. Although MSCs isolated from bone marrow have been shown to have chondrogenic potential, synovial membrane-derived MSCs (SM-MSCs) may have superior chondrogenic abilities due to a common progenitor cell between synovium and cartilage. The objective of this study was to directly compare the immunophenotype, proliferative capabilities, and chondrogenic potential of equine SM-MSCs and bone marrow-derived MSCs (BM-MSCs)...
Bertoni L, Branly T, Jacquet S, Desancé M, Desquilbet L, Rivory P, Hartmann DJ, Denoix JM, Audigié F, Galéra P, Demoor M.Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also ...
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. ...
Anderson JR, Jacobsen S, Walters M, Bundgaard L, Diendorfer A, Hackl M, Clarke EJ, James V, Peffers MJ.Extracellular vesicles comprise an as yet inadequately investigated intercellular communication pathway in the field of early osteoarthritis. We hypothesised that the small non-coding RNA expression pattern in synovial fluid and plasma would change during progression of experimental osteoarthritis. In this study, we conducted small RNA sequencing to provide a comprehensive overview of the temporal expression profiles of small non-coding transcripts carried by extracellular vesicles derived from plasma and synovial fluid for the first time in a posttraumatic model of equine osteoarthritis. Addi...
Gencoglu H, Orhan C, Sahin E, Sahin K.OA is quite common in companion animals, especially in large breed dogs and horses. Collagen, the most abundant protein of mammals, has specific connective tissue types for skin, bones, reticulate, basal lamina, bones, cell surfaces, while type II collagen (UC-II) forms the main structure of cartilage tissue. Even at the smaller dosages, UC-II has also been reported to be more effective than the glucosamine and chondroitin sulfate supplements, which are the supplements most frequently used in the market. In this review, we summarize the effects of UC-II on joint health and function in health a...
Salmonella enterica subsp. enterica serovar Abortusequi is frequently reported as a cause of abortion in mares and neonatal septicemia and polyarthritis in Asian and African countries, but only sporadically in Europe and the United States. We report an outbreak of S. Abortusequi in foals in Italy, characterized by high mortality. In a herd of Murgese horses, 10 of 34 newborns died at birth and a further 7 died, after developing severe clinical signs, during the first 10 d of life. Tissue specimens from different organs of 2 dead foals, synovial fluids from 4 sick foals, and vaginal and rectal ...
Manivong S, Cullier A, Audigié F, Banquy X, Moldovan F, Demoor M, Roullin VG.The burden of osteoarthritis (OA), one of the major causes of functional disabilities in humans and animals, continues to increase worldwide while no disease-modifying OA drugs (DMOADs) that either slow down or reverse disease progression have been made available. Here, we provide a brief overview of recent advances in: designing new OA drug delivery approaches, focusing on lubrication-based biomaterials and drug delivery systems, such as hydrogels, liposomes, dendrimers, micro- and nanoparticles; using either large (horse) or small (zebrafish) relevant animal models to evaluate new therapeuti...
Linardi RL, Dodson ME, Moss KL, King WJ, Ortved KF.Cartilage injury occurs commonly in equine athletes, often precipitating posttraumatic osteoarthritis (PTOA). Orthobiologics such as autologous conditioned serum (ACS) and autologous protein solution (APS) may be useful in decreasing posttraumatic inflammation, thereby preventing PTOA. The objective of this study was to quantify cytokine concentrations in ACS and APS and evaluate the protective effects of ACS and APS on inflamed chondrocytes cultured . We hypothesized that the combination of platelet-derived growth factors (PDGF) and anti-inflammatory cytokines present in APS would be superior...
Ishihara A, Shields KM, Litsky AS, Mattoon JS, Weisbrode SE, Bartlett JS, Bertone AL.This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-B...
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...
Hotham WE, Thompson C, Szu-Ting L, Henson FMD.Osteoarthritis (OA) in the horse is an economic and welfare issue and there are no current disease modifying drugs available. Stem cells have been suggested as a therapeutic intervention for OA, originally on the basis of their regenerative capacity. However, it is hypothesised that mesenchymal stem cells (MSC) exert their effects via paracrine factors including the production of extracellular vesicles that can themselves recapitulate the MSC effects in the joint. Objective: To isolate extracellular vesicles from bone marrow MSC and investigate their anti-inflammatory effects on chondrocytes. ...
Menendez MI, Clark DJ, Carlton M, Flanigan DC, Jia G, Sammet S, Weisbrode SE, Knopp MV, Bertone AL.To evaluate healing of surgically created large osteochondral defects in a weight-bearing femoral condyle in response to delayed percutaneous direct injection of adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6. Methods: Four 13mm diameter and 7mm depth circular osteochondral defects were drilled, 1/femoral condyle (n=20 defects in five ponies). At 2 weeks, Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline was percutaneously injected into the central drill hole of the defect. Quantitative magnetic resonance imaging (...
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...
Tyrnenopoulou P, Diakakis N, Karayannopoulou M, Savvas I, Koliakos G.Regenerative medicine has become one of the most promising therapies of equine osteoarthritis. Platelet lysate (PL) is rich in bioactive proteins and growth factors that play a crucial role in tissue healing. Objective: To evaluate the efficacy of intra-articularly injected autologous PL in equine athletes with naturally occurring osteoarthritis. Methods: Fifteen warmblood geldings aged 8-19 years with osteoarthritis of the distal interphalangeal joint were included in this study. They were randomly divided into two groups; 10 horses received intra-articular injections of PL and 5 of normal s...
Branly T, Bertoni L, Contentin R, Rakic R, Gomez-Leduc T, Desancé M, Hervieu M, Legendre F, Jacquet S, Audigié F, Denoix JM, Demoor M, Galéra P.Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the associ...
Ortved KF, Begum L, Mohammed HO, Nixon AJ.Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 10(5) AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were n...
