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.
Christmann U, Hancock CL, Poole CM, Emery AL, Poovey JR, Hagg C, Mattson EA, Scarborough JJ, Christopher JS, Dixon AT, Craney DJ, Wood PL.Horses with asthma or osteoarthritis frequently receive ω-3 fatty acid supplements. Docosahexaenoic (DHA; 22:6) and eicosapentaenoic (EPA; 20:5) acids are essential ω-3 fatty acid precursors of anti-inflammatory mediators and components of structural glycerophospholipids (GPL) that act as reservoirs of these fatty acids. Analysis of the incorporation of dietary DHA + EPA into GPL pools in different body compartments has not been undertaken in horses. We undertook a detailed study of dietary supplementation with DHA + EPA in horses and monitored incorporation into DHA- and EPA-contain...
Noordwijk KJ, Qin R, Diaz-Rubio ME, Zhang S, Su J, Mahal LK, Reesink HL.Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial fluid biomarkers could contribute to the diagnosis and understanding of osteoarthritis (OA) pathophysiology. Objective: The aim of this study was to identify differentially expressed metabolic and glycosylation pathways in synovial fluid from healthy horses and horses with naturally occurring carpal OA. Methods: Cross-sectional, in vivo metabolomics and glycomics study. Methods: In cohort 1, carpal synovial fluid (n = 12 horses...
Sigurdsson SF, Olstad K, Ley CJ, Björnsdóttir S, Griffiths DJ, Fjordbakk CT.Osteochondrosis occurs due to failure of the blood supply to growth cartilage. Osteochondrosis lesions have been identified in small tarsal bones and suggested to cause distal tarsal osteoarthritis; however, it has not been determined whether distal tarsal osteochondrosis lesions were the result of vascular failure. Objective: To perform post-mortem arterial perfusion and micro-computed tomography (CT) of the central (CTB) and third tarsal bones (TIII) of fetuses and foals up to 5 months old, to describe tarsal development and any lesions detected. Methods: Descriptive, nonconsecutive case se...
Somm F, Suárez Sánchez-Andrade J, Martens A, Zedler ST, Klopfenstein MD, Boswell JC, Bladon BM, Lischer CJ, Richardson DW, Auer JA, Fürst AE....To report on technical aspects and outcomes after scapulohumeral arthrodesis (SHA) with a locking compression plate (LCP) in small equids. Methods: Retrospective multicenter case series. Methods: Client-owned Shetland Ponies, Miniature Shetlands, and American Miniature Horses (n = 15). Methods: Inclusion criteria were completed SHA with an LCP to treat scapulohumeral osteoarthritis/subluxation and availability of postoperative radiographs. Contributing surgeons completed a questionnaire to collect data. All radiographs were reviewed for this study. Follow-up information was obtained via re-a...
Lee AKK, Uhl EW, Osborn ML.Therapies based upon whole-body biomechanical assessments are successful for injury prevention and rehabilitation in human athletes. Similar approaches have rarely been used to study equine athletic injury. Degenerative osteoarthritis caused by mechanical stress can originate from chronic postural dysfunction, which, because the primary dysfunction is often distant from the site of tissue injury, is best identified through modeling whole-body biomechanics. To characterize whole-body equine kinematics, a realistic skeletal model of a horse was created from equine computed tomography (CT) data t...
Camargo Garbin L, Morris MJ.Many alternative treatments aimed at modulating osteoarthritis (OA) progression have been developed in the past decades, including the use of cytokine inhibitors. IL-1β is considered one of the most impactful cytokines in OA disease and therefore, its blockage offers a promising approach for the modulation of OA. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory protein belonging to the IL-1 family that competes with IL-1β for occupancy of its receptors, without triggering the same downstream inflammatory response. Because of its natural anti-inflammatory ...
Elashry MI, Baulig N, Wagner AS, Klymiuk MC, Kruppke B, Hanke T, Wenisch S, Arnhold S.Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose-derived MSC morphology, viability, adherence, migration, and osteogenic differentiation. MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or...
Espinosa-Mur P, Phillips KL, Galuppo LD, DeRouen A, Benoit P, Anderson E, Shaw K, Puchalski S, Peters D, Kass PH, Spriet M.Cervical osteoarthritis (OA) has been documented as a potential source of pain and poor performance in sport horses. Objective: To assess the prevalence of cervical OA in a population of Warmblood jumpers and its correlation with age, level of performance, neck pain and mobility. Methods: Descriptive observational study. Methods: Warmblood jumpers free of lameness or neurological disorders were selected. Cervical pain and range of motion of the neck were subjectively assessed. Left to right lateral views were taken at C3-C4, C4-C5, C5-C6 and C6-C7. The presence of OA at the cervical articular ...
Castanheira C, Balaskas P, Falls C, Ashraf-Kharaz Y, Clegg P, Burke K, Fang Y, Dyer P, Welting TJM, Peffers MJ.Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potenti...
Bourdon B, Contentin R, Cassé F, Maspimby C, Oddoux S, Noël A, Legendre F, Gruchy N, Galéra P.Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen® hydrolyzed fish collagens from skin (Promerim®30 and Promerim®60) and cartilage (Promerim®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cyto...
Di Salvo A, Chiaradia E, Nannarone S, Della Rocca G.Joint pain is a major cause of lameness in animals such as horses and dogs, and it may affect their athletic performance and quality of life. The intra-articular administration of analgesic/antinflammatory drugs is a common practice in veterinary medicine, for both lameness diagnosis and joint pain management. It is used either perioperatively, such as in animals undergoing arthroscopy/arthrotomy, and in osteoarthritic animals. However, evidence regarding efficacy and safety of each drug is limited, and controversies persist in these areas. In particular, it is often uncertain whether a define...
Brown KA, Davidson EJ, Johnson AL, Wulster KB, Ortved K.Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. Objective: Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multipl...
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...
Kendall A, Nyström S, Ekman S, Hultén LM, Lindahl A, Hansson E, Skiöldebrand E.Nerve growth factor (NGF) is a neurotrophin with many functions. In humans, it is involved in inflammation, nerve growth, apoptosis and pain signalling. Increased concentrations of NGF in synovial fluid has been shown in humans and dogs with osteoarthritis. Despite osteoarthritis being a common problem in horses, no studies have previously been published on NGF in the equine joint. The aim of this study was to quantify NGF in equine synovial fluid from healthy joints, acutely inflamed septic joints and joints with structural changes associated with osteoarthritis. A secondary aim was to identi...
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 ...
Pritchard A, Nielsen BD, Robison C, Manfredi JM.As osteoarthritis is a major cause of lameness in horses in the United States, improving collagen health prior to onset and increasing collagen turnover within affected joints could improve health- and welfare-related outcomes. Through its positive effects on bone mineral content and density and its role in increasing collagen synthesis, silicon (Si) may slow the development and progression of osteoarthritis, thereby reducing lameness. This study evaluated the hypothesis that Si supplementation would increase cartilage turnover through increased collagen degradation and formation markers, as w...
da Silva Xavier AA, da Rosa PP, de Brum Mackmill L, Roll VFB.For several years, hyaluronic acid (HyA) and, more recently, polyacrylamide hydrogel (PHyd) have been used to reduce lameness and pain caused by osteoarthritis. However, there is still a lack of scientific evidence of the efficacy of these substances to allow veterinary experts to make decisions about their use in horses. The objective of this study was to evaluate, through a systematic review and network meta-analysis (NMA), the efficacy of HyA, associated or not with other drugs, and PHyd in relieving lameness in horses with osteoarthritis. The searches for primary studies were conducted on ...
Aleman M, Berryhill E, Woolard K, Easton-Jones CA, Kozikowski-Nicholas T, Dyson S, Kilcoyne I.Sidewinder gait in horses is poorly understood and characterized by walking with the trunk and pelvic limbs drifting to 1 side. Objective: To report causes, clinical and diagnostic features. Methods: Horses examined at 2 institutions. Methods: Retrospective study (2000-2019). Cases with sidewinder gait, neurological and orthopedic examination, and diagnostic work up or postmortem evaluation were included. Descriptive statistics were performed. Results: Twenty-four horses (mean age 18.9 years) of various breeds and both sexes were included. Onset was acute (N = 10), subacute (N = 6), and insi...
Balaskas P, Green JA, Haqqi TM, Dyer P, Kharaz YA, Fang Y, Liu X, Welting TJM, Peffers MJ.Ageing is a leading risk factor predisposing cartilage to osteoarthritis. However, little research has been conducted on the effect of ageing on the expression of small non-coding RNAs (sncRNAs). RNA from young and old chondrocytes from macroscopically normal equine metacarpophalangeal joints was extracted and subjected to small RNA sequencing (RNA-seq). Differential expression analysis was performed in R using package DESeq2. For transfer RNA (tRNA) fragment analysis, tRNA reads were aligned to horse tRNA sequences using Bowtie2 version 2.2.5. Selected microRNA (miRNAs or miRs) and small nucl...
Anderson JR, Phelan MM, Foddy L, Clegg PD, Peffers MJ.Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use. equine cartilage explants ( = 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-d...
Ramos S, Pinto A, Cardoso M, Alexandre N, Bettencourt E, Monteiro S, Gama LT.Radiographic prevalence and correlation of radiographic findings has not been performed in Lusitano Purebred horses. The aim of this study was to (1) evaluate the prevalence of primary osteoarthritis radiographic findings in Lusitano Purebred horses; (2) to assess correlations between radiographic findings in different joints of the same limb and different limbs; and (3) elucidate the effect of age in the radiographic findings. A radiographic protocol of the stifle, tarsi, fetlocks and distal limbs was done in 98 Lusitanos and the classification of the radiographs was performed using a 0-4 sc...
Jeremiasse B, Matta C, Fellows CR, Boocock DJ, Smith JR, Liddell S, Lafeber F, van Spil WE, Mobasheri A.Chondrocytes are exposed to an inflammatory micro-environment in the extracellular matrix (ECM) of articular cartilage in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA, degenerative changes and low-grade inflammation within the joint transform the behaviour and metabolism of chondrocytes, disturb the balance between ECM synthesis and degradation, and alter the osmolality and ionic composition of the micro-environment. We hypothesize that chondrocytes adjust their physiology to the inflammatory microenvironment by modulating the expression of cell surface prote...
Velloso Alvarez A, Boone LH, Pondugula SR, Caldwell F, Wooldridge AA.Autologous conditioned serum (ACS) and autologous protein solution (APS) are newer therapeutic options for osteoarthritis (OA). Co-culture of cartilage and synovium stimulated with IL-1β produces a similar physiologic response to tissues from naturally-ocurring OA. The study objective was to investigate the effects of ACS, APS, and triamcinolone (TA) on inflammatory and catabolic gene expression of inflamed joint tissues in co-culture. Blood was collected and processed for ACS and APS from six horses. Cartilage and synovial explants were harvested from the stifle, placed in co-culture, and tr...
Bertoni L, Jacquet-Guibon S, Branly T, Legendre F, Desancé M, Mespoulhes C, Melin M, Hartmann DJ, Schmutz A, Denoix JM, Galéra P, Demoor M....Osteoarthritis is a common cause of pain and economic loss in both humans and horses. The horse is recognized as a suitable model for human osteoarthritis, because the thickness, structure, and mechanical properties of equine articular cartilage are highly comparable to those of humans. Although a number of equine experimental osteoarthritis models have been described in the literature, these cases generally involve the induction of osteoarthritis in just one joint of each animal. This approach necessitates the involvement of large numbers of horses to obtain reliable data and thus limits the ...
Mostafa MB, Elemmawy YM.There is limited knowledge about causes of musculoskeletal injury in jumping Thoroughbred horses. The objective of this study was to describe the relationships between musculoskeletal disorders and linear and angular limb measurements acquired from photographs of horses with markers at specific reference points. The diagnosed musculoskeletal disorders in either fore or hind limbs were flexor tendonitis, suspensory ligaments desmitis, and osteoarthritis of the distal intertarsal and tarso-metatarsal and carpometacarpal joints. Lengths and angles in 17 clinically normal jumping Thoroughbred hors...
Kajabi AW, Casula V, Sarin JK, Ketola JH, Nykänen O, Te Moller NCR, Mancini IAD, Visser J, Brommer H, René van Weeren P, Malda J, Töyräs J....Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included ...
Bundgaard L, Stensballe A, Elbæk KJ, Berg LC.Similar to humans, the horse is a long-lived, athletic species. The use of mesenchymal stromal cells (MSCs) is a relatively new frontier, but has been used with promising results in treating joint diseases, e.g., osteoarthritis. It is believed that MSCs exert their main therapeutic effects through secreted trophic biomolecules. Therefore, it has been increasingly important to characterize the MSC secretome. It has been shown that the effect of the MSCs is strongly influenced by the environment in the host compartment, and it is a crucial issue when considering MSC therapy. The aim of this stud...
Casillas JM, Jacobs CC, Manfredi JM.To identify radiographic locations of soft tissue attachments in the tarsal region of horses and describe any variability in the gross anatomy of those attachments. Methods: 15 cadaveric limbs from 8 adult horses. Methods: 8 limbs were used for dissection and radiography of soft tissue structures, with metallic markers used to identify radiographic locations of soft tissue attachments. The remaining 7 limbs were used to evaluate anatomic variations in the insertion of the tendon of the fibularis tertius muscle. A consensus list of preferred radiographic views for evaluating each soft tissue at...
Matheson A, Regmi SC, Martin-Alarcon L, Jay GD, Scott WM, Schmidt TA.: In experimental models of equine joint-injury and osteoarthritis synovial fluid (SF) composition (proteoglycan-4, hyaluronan) can vary, along with changes to SF mechanical function (lubrication, viscosity). The study hypotheses were a) clinical equine joint-injury and disease results in altered SF composition and diminished mechanical function, and b) serum composition (proteoglycan-4 or hyaluronan) changes concurrently. The objectives were to characterize composition (proteoglycan-4, hyaluronan), and function of SF and serum from normal horses compared to clinical groups: osteoarthritis, ac...
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...
Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, Black SJ, Alfandari D.Equine laminitis is a debilitating disease affecting the digital laminae that suspend the distal phalanx within the hoof. While the clinical progression of the disease has been well documented, the molecular events associated with its pathogenesis remain largely unknown. Using real time quantitative PCR (RT-qPCR), we have investigated the expression of genes coding for proteins containing a Disintegrin and Metalloprotease domain (ADAM), as well as genes encoding the natural inhibitors of these enzymes (tissue inhibitor of metalloprotease; TIMP) in horses with naturally-acquired (acute, chronic...
McIlwraith CW.Intra-articular use of corticosteroids has become a recent focus (or re-focus) of attention in the Thoroughbred racing industry. This manuscript reviews the clinical use and scientific basis of intra-articular corticosteroid administration including catastrophic injury, articular cartilage degradation and the development of osteoarthritis (OA), as well as the timing of injection relative to racing.
Gustås P, Johnston C, Roepstorff L, Drevemo S.There is a high prevalence of lameness among Standardbred trotters, most commonly caused by noninfectious joint diseases, mainly related to training and competition. In this context, impact-related shock waves transmitted through the skeleton and joints have been proposed to be one important factor in the development of osteoarthritis. The aim of the present study was to investigate the characteristic pattern of the events immediately following first contact, with a focus on the in vivo transmission of impact shock waves in the distal forelimb. Two horses were trotted by hand over a force plat...
Bourdon B, Contentin R, Cassé F, Maspimby C, Oddoux S, Noël A, Legendre F, Gruchy N, Galéra P.Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen® hydrolyzed fish collagens from skin (Promerim®30 and Promerim®60) and cartilage (Promerim®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cyto...
Tung JT, Venta PJ, Caron JP.To determine the effects of recombinant equine IL-1beta and a number of antiinflammatory compounds on the expression and activity of inducible nitric oxide synthase (iNOS) in cultured equine chondrocytes. Methods: RT-PCR methods were used to amplify a portion of the equine iNOS message to prepare an RNA probe. Northern blot analysis was used to quantify the expression of iNOS in first passage cultures of equine articular chondrocytes propagated in the presence or absence of recombinant equine interleukin-1beta (reIL-1beta), dexamethasone (DEX), polysulfated glycosaminoglycan (PSGAG), hyalurona...
Bagge J, Berg LC, Janes J, MacLeod JN.Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSCs) have shown potential as cell-based therapies for cartilage and bone injuries and are used increasingly in human and veterinary practice to facilitate the treatment of orthopedic conditions. However, human and rodent studies have documented a sharp decline in chondrogenic and osteogenic differentiation potential with increasing donor age, which may be problematic for the important demographic of older orthopedic patients. The aim of this study was to identify the effect of donor age on the chondrogenic and osteog...
Christensen L, Camitz L, Illigen KE, Hansen M, Sarvaa R, Conaghan PG.Polyacrylamide hydrogel (PAAG) is a non-toxic, non-degradable synthetic product, used for years in the augmentation of soft tissues. Preliminary results in animals and humans have suggested long-lasting beneficial effects on symptoms of osteoarthritis (OA). The aim of this histopathological study was to investigate whether intra-articular injection of PAAG is integrated into synovial tissue in normal and OA animal joints, and if this integration is sustained. (A) A prospective, controlled, longitudinal study of normal knee joints injected with PAAG was performed in 10 rabbits, following the an...
Cohen JM, Richardson DW, McKnight AL, Ross MW, Boston RC.To (1) examine the outcome in horses with osteoarthritis or intra-articular soft tissue injuries of the stifle after arthroscopic exploration and debridement and (2) to determine any imaging or surgical findings that may influence prognosis. Methods: Case series. Methods: Horses (n=44) with lameness referable to the stifle, diagnosed with osteoarthritis, meniscal tears, or other intra-articular soft tissue injuries based on arthroscopic examination. Methods: Medical records of horses with stifle lameness that had arthroscopic exploration were reviewed. Horses with osteochondrosis lesions, intr...
Hurtig M, Pearce S, Warren S, Kalra M, Miniaci A.To investigate survival and function of autogenous heterotopic osteochondral grafts in a site where injuries are common. Methods: Three osteochondral grafts were harvested arthroscopically from the femoropatellar joint and transplanted to the third carpal bone (C(3)). Nine months later, histologic, histomorphometric, and biochemical comparisons were made between the transplanted grafts in C(3) and tissue adjacent to the recipient site, the opposing radial carpal bone (C(r)), the donor site in the femoropatellar joint, and the sham-operated contralateral C(3). Methods: One mixed-breed pony and ...
Peal BT, Gagliardi R, Su J, Fortier LA, Delco ML, Nixon AJ, Reesink HL.The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of equine joint injury affecting the carpal (wrist), tarsal (ankle), and femoropatellar (knee) joints. To establish ranges for lubricin, HA, and HA MW distributions across multiple joints, we first evaluated clinically healthy, high-motion equine joints. Synovial fluid was collected from high-motion joints in horses without clinical signs of joint disease (n = 11 horses, 102 joints) and from research horses undergoing carpal osteo...
Gold SJ, Werpy NM, Gutierrez-Nibeyro SD.Sagittal groove injuries of the proximal phalanx are an important cause of lameness in performance horses. The purpose of this retrospective case series study was to describe standing low-field magnetic resonance imaging (MRI) characteristics of these injuries in a group of Warmblood horses. Horses with an MRI diagnosis of sagittal groove injuries involving the proximal phalanx and that had follow-up MRI and clinical outcome information were included. Findings from clinical examinations, diagnostic tests, and other imaging modalities were recorded. All MRI studies were retrieved for re-evaluat...
McIlwraith CW, Frisbie DD, Kawcak CE.To assess clinical, radiographic, histologic, and biochemical effects of sodium pentosan polysulfate (NaPPS) administered IM for treatment of experimentally induced osteoarthritis in horses. Methods: 18 horses. Methods: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Nine horses received NaPPS (3 mg/kg, IM) on study days 15, 22, 29, and 36. Nine control horses received the same volume of saline (0.9% NaCl) solution IM on study days 15, 22, 29, and 36. Clinical, radiographic, gross, histologic, histochemical, and biochemical findings as well as findings of sy...
Laverty S, Lacourt M, Gao C, Henderson JE, Boyde A.We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC...
Svala E, Löfgren M, Sihlbom C, Rüetschi U, Lindahl A, Ekman S, Skiöldebrand E.The molecular aspects of inflammation were investigated in equine articular cartilage explants using quantitative proteomics. Articular cartilage explants were stimulated with interleukin (IL)-1β in vitro for 25 days, and proteins released into cell culture media were chemically labeled with isobaric mass tags and analyzed by liquid chromatography-tandem mass spectrometry. A total of 127 proteins were identified and quantified in media from explants. IL-1β-stimulation resulted in an abundance of proteins related to inflammation, including matrix metalloproteinases, acute phase proteins, comp...
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, ...
McD￮ LA, Esparza Gonzalez BP, Nino-Fong R, Aburto E.Autologous mesenchymal stem cells (MSCs) have been used as a potential cell-based therapy in various animal and human diseases. Their differentiation capacity makes them useful as a novel strategy in the treatment of tissue injury in which the healing process is compromised or delayed. In horses, bone healing is slow, taking a minimum of 6-12 months. The osteogenic capacity of equine bone marrow and muscle MSCs mixed with fibrin glue or phosphate-buffered saline (PBS) as a scaffold is assessed. Bone production by the following groups was compared: Group 1, bone marrow (BM) MSCs in fibrin glue;...
Contino EK.Joint disease is one of the most common issues effecting sport horses. Because there is no cure for joint disease, treatment goals surround slowing progression of the disease, minimizing pain, increasing function, and optimizing performance. Accomplishing these goals often requires a multimodal approach that combines systemic medications or supplements; intra-articular therapies, such as corticosteroids or biologics; management considerations; and physical therapy exercises.
Ishihara A, Bartlett JS, Bertone AL.Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vit...
Novakofski KD, Williams RM, Fortier LA, Mohammed HO, Zipfel WR, Bonassar LJ.Cartilage injury can lead to post-traumatic osteoarthritis (PTOA). Immediate post-trauma cellular and structural changes are not widely understood. Furthermore, current cellular-resolution cartilage imaging techniques require sectioning of cartilage and/or use of dyes not suitable for patient imaging. In this study, we used multiphoton microscopy (MPM) data with FDA-approved sodium fluorescein to identify and evaluate the pattern of chondrocyte death after traumatic injury. Methods: Mature equine distal metacarpal or metatarsal osteochondral blocks (OCBs) were injured by 30 MPa compressive loa...
Löfgren M, Svala E, Lindahl A, Skiöldebrand E, Ekman S.Osteoarthritis is an inflammatory and degenerative joint disease commonly affecting horses. To identify genes of relevance for cartilage pathology in osteoarthritis we studied the time-course effects of interleukin (IL)-1β on equine articular cartilage. Articular cartilage explants from the distal third metacarpal bone were collected postmortem from three horses without evidence of joint disease. The explants were stimulated with IL-1β for 27 days and global gene expression was measured by microarray. Gene expression was compared to that of unstimulated explants at days 3, 9, 15, 21 and 27...
Kulin RM, Jiang F, Vecchio KS.Although clinical bone fractures occur predominantly under impact loading (as occurs during sporting accidents, falls, high-speed impacts or other catastrophic events), experimentally validated studies on the dynamic fracture behavior of bone, at the loading rates associated with such events, remain limited. In this study, a series of tests were performed on femoral specimens obtained post-mortem from equine donors ranging in age from 6 months to 28 years. Fracture toughness and compressive tests were performed under both quasi-static and dynamic loading conditions in order to determine the ef...
Fietz S, Einspanier R, Hoppner S, Hertsch B, Bondzio A.Matrix metalloproteinases (MMPs)-2 and -9 activities have been found elevated in synovial fluid from various joint diseases in man. However, in the horse few data are available. Objective: To explore the clinical significance of MMP-2 and -9 activities in synovial fluid of horses with different forms of joint diseases. Methods: Gelatin zymography and MMP-2 and -9 immunocapture activity assays were applied on synovial fluids from control joints and joints with aseptic joint disease (AJD) and septic arthritis (SA). Additionally, MMP-2 and -9 activities were measured in samples from SA to monitor...
Cantley CE, Firth EC, Delahunt JW, Pfeiffer DU, Thompson KG.This study identified changes consistent with osteoarthritis; articular cartilage damage, subchondral bone sclerosis and marginal osteophytes, in the metacarpophalangeal joints of wild New Zealand horses. The articular cartilage lesions were identified by Indian ink staining techniques and histology. The lesions occurred on the proximodorsal aspect of the first phalanx (P1) and were more severe on the medial compared to the lateral eminence of the bone, and their severity increased with age. The bone mineral density of the subchondral bone underlying the cartilage lesions, assessed using conve...
Milner PI, Clegg PD, Stewart MC.This article provides an overview of the cellular and molecular events involved in bone repair and the current approaches to using stem cells as an adjunct to this process. The article emphasizes the key role of osteoprogenitor cells in the formation of bone and where the clinical applications of current research may lend themselves to large animal orthopaedics. The processes involved in osteogenic differentiation are presented and strategies for bone formation, including induction by osteogenic factors, bioscaffolds, and gene therapy, are reviewed.
Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY.Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte apoptosis has been implicated as a major pathological OA change in humans and experimental animals but no studies have been performed on equine OA. Articular cartilage was collected from three normal and five OA horses. Histopathological changes were scored by a modified Mankin grading system. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from chondrocytes was indirectly evaluated by immunohistochemistr...
Kawcak CE, Frisbie DD, McIlwraith CW.To evaluate effects of extracorporeal shock wave therapy (ESWT) and polysulfated glycosaminoglycan treatment (PSGAGT) on subchondral bone (SCB), serum biomarkers, and synovial fluid biomarkers in horses with induced osteoarthritis. Methods: 24 healthy 2- to 3-year-old horses. Methods: An osteochondral fragment was created on the distal aspect of the radial carpal bone in 1 middle carpal joint of each horse. Horses were randomly allocated to receive local application of ESWT (days 14 and 28; n = 8), PSGAGT (IM, q 4 d for 28 days; 8), or a sham ESWT probe (placebo; days 14 and 28; 8). Serum biom...
Spaas JH, Broeckx SY, Chiers K, Ferguson SJ, Casarosa M, Van Bruaene N, Forsyth R, Duchateau L, Franco-Obregón A, Wuertz-Kozak K.Clinical results of regenerative treatments for osteoarthritis are becoming increasingly significant. However, several questions remain UNANSWERED concerning mesenchymal stem cell (MSC) adhesion and incorporation into cartilage. Methods: To this end, peripheral blood (PB) MSCs were chondrogenically induced and/or stimulated with pulsed electromagnetic fields (PEMFs) for a brief period of time just sufficient to prime differentiation. In an organ culture study, PKH26 labelled MSCs were added at two different cell densities (0.5 x106 vs 1.0 x106). In total, 180 explants of six horses (30 per hor...
Vandeweerd JM, Zhao Y, Nisolle JF, Zhang W, Zhihong L, Clegg P, Gustin P.Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and bioc...
Ortved KF, Begum L, Stefanovski D, Nixon AJ.Following joint trauma, a posttraumatic inflammatory cascade drives degeneration of the joint. We aimed to assess whether transduction of chondrocytes with AAV5 overexpressing the immunomodulatory cytokine IL-10 would have protective effects in pellet cultures stimulated with IL-1β. Chondrocytes were isolated from 3 healthy horses and were transduced with AAV5-IL-10 at a dose of 1 x 105vg/cell. Chondrocyte pellets were formed by centrifugation and were stimulated with IL-1β starting 48 hours following transduction. After 2, 6 and 14 days in culture, supernatants were collected for cytokine a...
Ley C, Ekman S, Elmén A, Nilsson G, Eloranta ML.The carpal joints are common sites of traumatic arthritis and osteoarthritis (OA) in athletic horses. The pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF) may be of great importance in the development of intra-articular lesions. The aim of the present study was to investigate possible associations between synovial fluid levels of bioactive IL-6 and TNF and different types of joint lesions seen in traumatic arthritis and OA. Synovial fluid was collected from horses with carpal lameness immediately before arthroscopic surgery. Articular cartilage, synovial membranes...
