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.
Fukuda K, Mita H, Tamura N, Kuroda T, Kuwano A, Takahashi T, Sato F.Persistent synovitis damages the articular cartilage in horses. To evaluate the effectiveness of treatment for synovitis using a model induced by intra-articular administration of monoiodoacetic acid (MIA), it is necessary to identify inflammatory biomarkers characteristic of the MIA model. Synovitis was induced by administering MIA into the unilateral antebrachiocarpal joints of five horses, and saline was injected into the contralateral joints as a control on day 0. Clinical and ultrasonographic examinations and synovial fluid collection were performed on days 0, 1, 2, 7, 14, 21, 28, and 35....
Yassin AM, AbuBakr HO, Abdelgalil AI, Farid OA, El-Behairy AM, Gouda EM.One of the most orthopedic problems seen in the equine is osteoarthritis (OA). The present study tracks some biochemical, epigenetic, and transcriptomic factors along different stages of monoiodoacetate (MIA) induced OA in donkeys in serum and synovial fluid. The aim of the study was the detection of sensitive noninvasive early biomarkers. OA was induced by a single intra-articular injection of 25 mg of MIA into the left radiocarpal joint of nine donkeys. Serum and synovial samples were taken at zero-day and different intervals for assessment of total GAGs and CS levels as well as miR-146b, m...
Kendall A, Lützelschwab C, Lundblad J, Skiöldebrand E.Nerve growth factor (NGF) is a neurotrophin that is increased in osteoarthritic joints of horses. In humans, NGF has been associated with pain, and both synovial and serum NGF concentrations are increased in osteoarthritic patients. Studies in humans also have shown that serum NGF concentration can increase with stress. Serum NGF concentration should be evaluated in horses with osteoarthritis-associated lameness. Objective: Quantify and compare serum NGF concentration in horses with osteoarthritis-associated lameness and sound horses. Additionally, the impact of short-term stress on serum NGF ...
O'Brien TJ, Hollinshead F, Goodrich LR.Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play...
Seewald LA, Sabino IG, Montney KL, Delco ML.To evaluate mitochondrial DNA (mtDNA) release from injured chondrocytes and investigate the utility of synovial fluid mtDNA concentration in early detection of posttraumatic osteoarthritis. We measured mtDNA release using four models of osteoarthritis: in vitro interleukin-1β stimulation of cultured equine chondrocytes, ex vivo mechanical impact of bovine cartilage explants, in vivo mechanical impact of equine articular cartilage, and naturally occurring equine intraarticular fracture. In our in vivo model, one group was treated with an intraarticular injection of the mitoprotective peptide S...
Brown KA, Davidson EJ, Johnson AL, Stefanovski D, Wulster KB, Ortved K.Caudal cervical articular process joint osteoarthritis (CAPJ OA) leads to career-altering clinical signs in the horse. Oblique radiographs and standing cone beam computed tomography (CBCT) facilitate the assessment of this area, however, the variability of interpretation of these images is currently unknown. This retrospective, secondary analysis, methods comparison study investigated interobserver agreement between clinicians and modality in grades of CAPJ OA on lateral and oblique radiographs and CBCT. We hypothesized that agreement between clinicians' grades of CAPJ OA would be lowest for o...
Andrietti ALP, Durgam SS, Naumann B, Stewart M.Mesenchymal stem cells are characterized by their capacities for extensive proliferation through multiple passages and, classically, tri-lineage differentiation along osteogenic, chondrogenic and adipogenic lineages. This study was carried out to compare osteogenesis in equine bone marrow-, synovium- and adipose-derived cells, and to determine whether osteogenic capacity is reflected in the basal expression of the critical osteogenic transcription factors Runx2 and Osterix. Unassigned: Bone marrow, synovium and adipose tissue was collected from six healthy 2-year-old horses. Cells were isolate...
Adepu S, Lord M, Hugoh Z, Nyström S, Mattsson-Hulten L, Abrahamsson-Aurell K, Lützelschwab C, Skiöldebrand E.We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. Unassigned: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N = 19) and OA horses (N = 9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluat...
Panizzi L, Dittmer KE, Vignes M, Doucet JS, Gedye K, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Riley CB.Biomarkers for osteoarthritis (OA) in horses have been extensively investigated, but translation into clinical use has been limited due to cost, limited sensitivity, and practicality. Identifying novel biomarkers that overcome these limitations could facilitate early diagnosis and therapy. This study aimed to compare the concentrations of synovial fluid (SF) and plasma cell-free DNA (cfDNA) over time in control horses with those with induced carpal OA. Following an established model, unilateral carpal OA was induced in 9 of 17 healthy Thoroughbred fillies, while the remainder were sham-operate...
Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Käkelä R, Niemelä T, Mykkänen A, Sihvo SP, Nieminen P.Individual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexp...
Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R.The metacarpophalangeal joint undergoes enormous loading during locomotion and can therefore often become inflamed, potentially resulting in osteoarthritis (OA). There are studies indicating that the endocannabinoid system (ECS) modulates synovium homeostasis, and could be a promising target for OA therapy. Some cannabinoid receptors, which modulate proliferative and secretory responses in joint inflammation, have been functionally identified in human and animal synovial cells. Unassigned: To characterize the cellular distribution of the cannabinoid receptors 1 (CB1R) and 2 (CB2R), and the can...
Ciamillo SA, Pownder SL, Potter HG, Stefanovski D, Nixon AJ, Ortved KF.Injury of articular cartilage is common, and due to the poor intrinsic capabilities of chondrocytes, it can precipitate joint degradation and osteoarthritis (OA). Implantation of autologous chondrocytes into cartilaginous defects has been used to bolster repair. Accurate assessment of the quality of repair tissue remains challenging. This study aimed to investigate the utility of noninvasive imaging modalities, including arthroscopic grading and optical coherence tomography (OCT) for assessment of early cartilage repair (8 weeks), and MRI to determine long-term healing (8 months). Large (15 mm...
Mayet A, Zablotski Y, Roth SP, Brehm W, Troillet A.Equine veterinarians face challenges in treating horses with osteoarthritic joint pain in routine veterinary practice. All common treatment options aim to reduce the clinical consequences of osteoarthritis (OA) characterized by persistent synovitis and progressive degradation of articular cartilage. A range of joint-associated cell types and extracellular matrices are involved in the not yet entirely understood chronic inflammatory process. Regeneration of articular tissues to re-establish joint hemostasis is the future perspective when fundamental healing of OA is the long-term goal. The use ...
Keller LE, Tait Wojno ED, Begum L, Fortier LA.Infiltration of cluster of differentiation (CD) 3 (CD3) T cells into the synovium and synovial fluid occurs in most patients with posttraumatic osteoarthritis. During disease progression, proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells infiltrate the joint in response to inflammation. This study aimed to characterize the dynamics of regulatory T and T helper 17 cell populations in synovial fluid from equine clinical patients with posttraumatic osteoarthritis to determine whether phenotype and function are associated with potential immunotherapeutic targets. An imbala...
Jammes M, Contentin R, Cassé F, Galéra P.Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry....
Teti G, Mazzotti E, Gatta V, Chiarini F, Alfieri ML, Falconi M.Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we ai...
Kaneps AJ.Regenerative medicine therapies have become significant tools for treatment of joint, soft tissue, and a variety of other conditions in animals and humans. Regenerative medicine aims to restore form and function of injured tissues using the body's own resources such as cells, fluids (ie, plasma and serum), and their resulting anti-inflammatory and prohealing cytokines. Platelet-rich plasma and other hemoderivatives have application for joint disorders such as osteoarthritis, cartilage injury, synovitis, and soft tissue injuries. These therapies achieve anti-inflammatory and healing effects wit...
Fadel C, Giorgi M.According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in...
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...
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 ...
Boorman S, Hanson RR, Velloso Alvarez A, Zhong K, Hofmeister E, Boone LH.To determine the effect of concurrent versus delayed treatment with corticosteroid on equine articular tissues also treated with local anesthetic in vitro in the presence of inflammatory mediators. Methods: Controlled laboratory study. Methods: Five geldings, one mare (aged 3-18 years). Methods: From each horse, 24 synovial and 12 osteochondral explants were cultured in a 12-well plate (2 wells/group, 2 synovial and 1 osteochondral explant/well, total 216 explants in the study). Explants were stimulated in culture medium with 10 μg/ml recombinant equine interleukin-1β and 10 μg/ml tumor...
Baker ME, Lee S, Clinton M, Hackl M, Castanheira C, Peffers MJ, Taylor SE.Osteoarthritis of the equine distal interphalangeal joint is a common cause of lameness. MicroRNAs from biofluids are promising biomarkers and therapeutic candidates. Synovial fluid samples from horses with mild and severe equine distal interphalangeal joint osteoarthritis were submitted for small RNA sequencing. The results demonstrated that miR-92a was downregulated in equine synovial fluid from horses with severe osteoarthritis and there was a significant increase in COMP, COL1A2, RUNX2 and SOX9 following miR-92a mimic treatment of equine chondrocytes in monolayer culture. This is the first...
Taguchi T, Morales Yniguez FJ, Takawira C, Andrews FM, Lopez MJ.Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, an...
Zielińska P, Śniegucka K, Kiełbowicz Z.The aim of this work was to characterize and describe the effect of High Intensity Laser Therapy (HILT) used in the treatment of chronic osteoarthritis in horses. Over a 2 year period, 11 horses with diagnosed bone spavin were treated with HILT as a monotherapy. The horses chosen for this report presented hind limb lameness, were positive in a spavin flexion test and showed improvement after intra-articular anesthesia of the tarsometatarsal joint. Additionally, all the horses presented radiological signs of tarsus osteoarthritis and had not been treated for bone spavin for a minimum of 6 month...
Baker ME, Kershaw LE, Carstens A, Daniel CR, Brown H, Roberts S, Taylor SE.Low-field magnetic resonance imaging (MRI) is widely available to equine veterinarians yet is insensitive at detecting cartilage damage in the distal interphalangeal joint (DIPJ). T2 mapping is a quantitative imaging technique that can detect cartilage damage before morphological change is apparent. Objective: Validation of a T2 mapping sequence on a low-field MR system. Correlation of the mean T2 relaxation time in sections of cartilage with varying levels of pathology using low- and high-field MRI. Methods: Cross-sectional study. Methods: Eight phantoms with known (nominal) T2 values underwe...
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...
Boström A, Asplund K, Bergh A, Hyytiäinen H.To explore the scientific evidence for therapeutic ultrasound (TU), we conducted a systematic review of the literature on TU in dogs, horses, donkeys, and cats. Methods: In three major databases, relevant articles published in 1980-2020 were identified. The risk of bias in each article was evaluated. Results: Twenty-four relevant articles on the effects of TU in dogs, nine in horses, two in donkeys, and one in cats were identified. TU usually involved 2-6 treatments weekly for up to 4 weeks. Articles on tendon, ligament, and bone healing, acute aseptic arthritis, osteoarthritis, paraparesis, h...
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 ...
Boström A, Bergh A, Hyytiäinen H, Asplund K.Extracorporeal shockwave therapy (ECSWT) is increasingly used to treat different types of musculoskeletal conditions in sport and companion animals. To explore the scientific basis for the treatment, we conducted a systematic review of the literature on ECSWT used in horses, dogs, and cats. Methods: Relevant articles published in 1980-2020 were identified from three major databases. Each article was assessed for risk of bias. Results: The review identified 27 relevant articles on the effects of ECSWT in horses, nine in dogs, but none in cats. Typically, ECSWT involved one to three treatment se...
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...
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...
Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ.A gene therapeutic approach to treat osteoarthritis (OA) appears to be on the horizon for millions of people who suffer from this disease. Previously we described optimization of a scAAVIL-1ra gene therapeutic vector and initially tested this in an equine model verifying long-term intrasynovial IL-1ra protein at therapeutic levels. Using this vector, we carried out a dosing trial in six horses to verify protein levels and establish a dose that would express relevant levels of therapeutic protein for extended periods of time (8 months). A novel arthroscopic procedure used to detect green fluore...
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...
Murata D, Miyakoshi D, Hatazoe T, Miura N, Tokunaga S, Fujiki M, Nakayama K, Misumi K.Cartilage regeneration with cell therapy following arthroscopic surgery could be used in racehorses with intra-articular fractures (IAF) and osteochondritis dissecans (OCD). The aims of this study were to investigate the origin and multipotency of stromal cells in the synovial fluid (SF) of horses with intra-articular injury and synovitis, and to provide a new strategy for regeneration of lost articular cartilage. Mesenchymal stromal cells were isolated from SF of horses with IAF and OCD. Multipotency was analysed by RT-PCR for specific mRNAs and staining for production of specific extracellul...
Anderson JR, Phelan MM, Clegg PD, Peffers MJ, Rubio-Martinez LM.Osteoarthritis (OA), osteochondrosis (OC), and synovial sepsis in horses cause loss of function and pain. Reliable biomarkers are required to achieve accurate and rapid diagnosis, with synovial fluid (SF) holding a unique source of biochemical information. Nuclear magnetic resonance (NMR) spectroscopy allows global metabolite analysis of a small volume of SF, with minimal sample preprocessing using a noninvasive and nondestructive method. Equine SF metabolic profiles from both nonseptic joints (OA and OC) and septic joints were analyzed using 1D H NMR spectroscopy. Univariate and multivariate ...
Olive J, D'Anjou MA, Alexander K, Laverty S, Theoret C.We compared the ability of 1.5 T magnetic resonance imaging (MRI), computed tomography (CT), and computed radiography (CR) to evaluate noncartilaginous structures of the equine metacarpophalangeal joint (MCP), and the association of imaging changes with gross cartilage damage in the context of osteoarthritis. Four CR projections, helical single-slice CT, and MRI (Ti-weighted gradient recalled echo [GRE], T2*-weighted GRE with fast imaging employing steady-state acquisition [FIESTA], T2-weighted fast spin echo with fat saturation, and spoiled gradient recalled echo with fat saturation ISPGR-FS]...
Todhunter PG, Kincaid SA, Todhunter RJ, Kammermann JR, Johnstone B, Baird AN, Hanson RR, Wright JM, Lin HC, Purohit RC.To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone. Methods: 2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2). Methods: Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articula...
Zimmerman M, Dyson S, Murray R.There has been no objective study comparing radiological features of spinous processes (SPs) in the thoracolumbar region and/or scintigraphic findings with clinical signs. Objective: To investigate the relationship between the presence or absence of clinical signs of back pain and: 1) radiological findings of close, impinging or overriding SPs; 2) increased radiopharmaceutical uptake (IRU) in the SPs; and 3) the combination of radiological findings and IRU. Also to determine the prevalence of concurrent osseous pathology. Methods: Five-hundred and eighty-two horses, presented for perceived bac...
Boehm AK, Seth M, Mayr KG, Fortier LA.Many metabolic processes in chondrocytes thought to contribute to age-related changes in the extracellular matrix are influenced by known roles of Hsp90. Age-related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin-like growth factor 1 (IGF-1) and interleukin-1beta (IL-1beta) signaling in chondrocytes. Methods: Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real-time polymerase chain rea...
Zayed MN, Schumacher J, Misk N, Dhar MS.Mesenchymal stromal cells (MSCs) have the capacity to differentiate into cells of mesenchymal lineage, such as chondrocytes, and have potential for use in regeneration of equine articular cartilage. MSCs instilled intra-articularly would be exposed to the inflamed environment associated with equine osteoarthritis (OA), which may compromise their function and ability to heal a cartilaginous defect. The aim of this study was to assess the ability of equine adult MSCs to differentiate into chondrocytes when stimulated with pro-inflammatory cytokines. MSCs derived from equine bone marrow (BM) and ...
van den Boom R, van de Lest CH, Bull S, Brama RA, van Weeren PR, Barneveld A.The importance of osteoarthritis (OA) in the horse and the difficulty in its early diagnosis have led to a search for potential biomarkers of joint disease. If the levels of such markers are to be interpreted accurately, clinicians and researchers need to know whether they are influenced by environmental factors and/or interventions such as exercise and repeated arthrocentesis. Objective: To investigate the influence of repeated arthrocentesis and exercise on nitric oxide (NO), prostaglandin E2 (PGE2) and glycosaminoglycan (GAG) concentrations in synovial fluid (SF) from normal equine joints. ...
David F, Farley J, Huang H, Lavoie JP, Laverty S.To evaluate mRNA expression of several proinflammatory and anti-inflammatory cytokines and chemokines in equine unstimulated and interleukin-1beta (IL-1beta)-stimulated chondrocytes. Methods: In vitro experiment using equine chondrocyte cultures. Methods: Whole articular cartilage from metacarpophalangeal joints (n=5 horses; 10 fetlocks). Methods: Chondrocyte monolayer cultures were established from digested adult equine articular cartilage and stimulated with 5 ng/mL of recombinant human IL-1beta. RNA was extracted from the cells 24 hours after stimulation. IL-1beta, IL-4, IL-6, IL-8, tumor n...
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...
Sarin JK, Te Moller NCR, Mancini IAD, Brommer H, Visser J, Malda J, van Weeren PR, Afara IO, Töyräs J.Arthroscopic assessment of articular tissues is highly subjective and poorly reproducible. To ensure optimal patient care, quantitative techniques (e.g., near infrared spectroscopy (NIRS)) could substantially enhance arthroscopic diagnosis of initial signs of post-traumatic osteoarthritis (PTOA). Here, we demonstrate, for the first time, the potential of arthroscopic NIRS to simultaneously monitor progressive degeneration of cartilage and subchondral bone in vivo in Shetland ponies undergoing different experimental cartilage repair procedures. Osteochondral tissues adjacent to the repair sites...
Kremer A, Ribitsch I, Reboredo J, Dürr J, Egerbacher M, Jenner F, Walles H.Meniscal injuries are the most frequently encountered soft tissue injuries in the equine stifle joint. Due to the inherent limited repair potential of meniscal tissue, meniscal injuries do not only affect the meniscus itself but also lead to impaired joint homeostasis and secondary osteoarthritis. The presented study compares 3D coculture constructs of primary equine mesenchymal stem cells (MSC) and meniscus cells (MC) seeded on three different scaffolds-a cell-laden collagen type I hydrogel (Col I gel), a tissue-derived small intestinal matrix scaffold (SIS-muc) and a combination thereof-for ...
Malekipour F, Whitton C, Oetomo D, Lee PV.Despite the important role of subchondral bone in maintaining the integrity of the overlying articular cartilage, little research has focused on measuring its mechanical behavior, particularly under injurious load conditions such as impact compression. In this study, the stiffness and the absorbed energy of subchondral bone were compared to that of its overlying cartilage by applying impact compression to equine cartilage-bone specimens. Deformations of the cartilage and subchondral bone were examined independently within the cartilage-bone unit by analyzing real-time images of cartilage-bone ...
Norrdin RW, Kawcak CE, Capwell BA, McIlwraith CW.Gross examination of metacarpo-/metatarsophalangeal (fetlock) joints from racehorses revealed defects on the condylar surface that ranged from cartilage fibrillation and erosion to focal cartilage indentations and cavitation in subchondral bone characteristic of traumatic osteochondrosis. Because these lesions represented a spectrum of mechanically induced arthrosis in which microdamage is thought to play a role, a histologic study of sagittal sections was made to study the morphogenesis. Subchondral bone failure developed beneath a flattened section of the condyle where the margin of the sesa...
Revenaugh MS.Veterinarians have begun using extracorporeal shock wave therapy (ESWT) for treatment of osteoarthritis (OA) in horses, although relatively little information has been published about its efficacy or mechanism of action. As a clinician, it can be difficult to know if and when ESWT should be recommended. Case studies in which ESWT is used to treat advanced OA in horses are discussed. ESWTseems to be a valuable adjunct for management of equine OA. It is the purpose of this article to discuss indications and techniques as well as to share clinical experiences using ESWT in the treatment of OA in ...
Mariñas-Pardo L, García-Castro J, Rodríguez-Hurtado I, Rodríguez-García MI, Núñez-Naveira L, Hermida-Prieto M.Osteoarthritis commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose-derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days o...
Rakic R, Bourdon B, Hervieu M, Branly T, Legendre F, Saulnier N, Audigié F, Maddens S, Demoor M, Galera P.As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM). To enhance the MACI therapy efficiency, we have developed a strategy for chondrocyte redifferentiation, and demonstrated its feasibility in the equine model. Thus, to mimic the cartilage microe...
Svala E, Jin C, Rüetschi U, Ekman S, Lindahl A, Karlsson NG, Skiöldebrand E.The glycoprotein lubricin contributes to the boundary lubrication of the articular cartilage surface. The early events of osteoarthritis involve the superficial layer where lubricin is synthesised. Objective: To characterise the glycosylation profile of lubricin in synovial fluid from horses with osteoarthritis and study secretion and degradation of lubricin in an in vitro inflammation cartilage model. Methods: In vitro study. Methods: Synovial fluid samples collected from horses with joints with normal articular cartilage and structural osteoarthritic lesions; with and without osteochondral f...
Tung JT, Arnold CE, Alexander LH, Yuzbasiyan-Gurkan V, Venta PJ, Richardson DW, Caron JP.To determine the effects of prostaglandin E2 (PGE2) on recombinant equine interleukin (IL)-1beta-stimulated expression of matrix metalloproteinases (MMP 1, MMP 3, MMP 13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in vitro. Methods: Cultured equine chondrocytes. Methods: Stationary monolayers of first-passage chondrocytes were exposed to graduated concentrations of PGE2 with or without a subsaturating dose (50 pg/ml) of recombinant equine IL-1beta (reIL-1beta) to induce expression of MMP 1, MMP 3, MMP 13, and TIMP 1, followed by RNA isolation and northern blotting. In subseque...
Carmona JU, Ríos DL, López C, Álvarez ME, Pérez JE, Bohórquez ME.Platelet-rich plasma (PRP) preparations are a common treatment in equine osteoarthritis (OA). However, there are controversies regarding the ideal concentration of platelets and leukocytes in these biological substances necessary to induce an adequate anti-inflammatory and anabolic response in articular cartilage. The aims were to study the influence of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the histological changes of cartilage, the degree of chondrocyte apoptosis, the production of hyaluronan (HA) and the gene expression of nuclear factor ...
Huser CA, Peacock M, Davies ME.Chondrocyte death, a notable feature of osteoarthritis, may play a role in the initiation of cartilage degeneration. The present study was aimed at uncovering the nature and involvement of cell death in the initiation of cartilage degeneration induced by mechanical trauma. Methods: Articular cartilage discs obtained from healthy skeletally mature horses were subjected to a single-impact load (500 g from 50 mm) using a simple drop-tower device and cultured in vitro for 48 h. Chondrocyte death was examined using two independent methods: transmission electron microscopy and caspase-3 activity ass...
Mirza MH, Bommala P, Richbourg HA, Rademacher N, Kearney MT, Lopez MJ.Mechanisms to reduce lameness associated with osteoarthritis (OA) are vital to equine health and performance. This study was designed to quantify response to autologous, intra-articular platelet-rich plasma (PRP) in horses with OA. Kinetic gait analysis was performed on 12 horses with unilateral forelimb lameness and OA in the same limb before and after intra-articular anesthesia (IAA). Radiographs and kinetic data were obtained before and 6 and 16 weeks after PRP administration to same joint, 4 weeks after IAA. Statistical evaluations included filtration effect on platelet concentration, ...
Huser CA, Davies ME.The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium wa...
Gupta RC, Canerdy TD, Skaggs P, Stocker A, Zyrkowski G, Burke R, Wegford K, Goad JT, Rohde K, Barnett D, DeWees W, Bagchi M, Bagchi D.The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same sur...
Tew SR, McDermott BT, Fentem RB, Peffers MJ, Clegg PD.Messenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome-wide posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes. Methods: Human articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels ...
Boyce MK, Trumble TN, Carlson CS, Groschen DM, Merritt KA, Brown MP.Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods: An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) ...
