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.
Kwon YS, Jeong H, Kim J, Kim J, Chun K, Yang SK, Kim B.Osteoarthritis is a leading cause of equine lameness, yet pragmatic evidence for nutraceuticals in horses remains limited. Unassigned: We prospectively evaluated 12 weeks of daily natural eggshell membrane (NEM; 12 mg/kg, orally) supplementation in Warmblood horses with chronic lameness using a single-arm before-after design. Ten horses were enrolled and prespecified paired contrasts compared visit 3 (V3, week 12) with baseline (V1). Outcomes included rider-reported under-saddle function (walk and trot), examiner-graded lameness (rest and walk-trot composite), simple joint-angle kinematics...
Skierbiszewska K, Turek B, Jasiński T, Kaczorowski M, Kozłowska N, Higuchi J, Domino M.Bone grafting in equine medicine offers a promising contribution to treating orthopaedic developmental diseases and chondral, osteochondral and segmental bone defects. Among grafts, synthetic bone substitutes-alloplastics-show favourable biological properties addressing numerous limitations presented by autografts, xenografts and allografts. Objective: To compile and disseminate clinical data and research findings from existing publications on the use of alloplastics in horses. Methods: Systematic review. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis 202...
Schmidt S, Swagemakers JH, le Jeune SS.The cervical vertebral column in horses plays a crucial role in movement, posture, and performance and disorders affecting it can cause pain, ataxia, or lameness. This review discusses major acquired (traumatic, infectious, neoplastic) and degenerative (osteoarthritis, foraminal stenosis, intervertebral disc disease) conditions. Acquired lesions often arise from trauma, bacterial infection, or neoplasia, with clinical signs ranging from neck pain to neurologic deficits. Degenerative disorders, particularly osteoarthritis of articular process joints, are common in the caudal cervical spine and ...
Bosman LM, Logan MG, Miszewski A, Pepper MS.Translational regenerative medicine, integrating human and veterinary approaches within the "One Health" framework, increasingly uses horses as models for human musculoskeletal conditions due to shared anatomical and functional features. Osteoarthritis and tendon disorders affect both species, often resulting from high-impact or repetitive strain activities. Regenerative medicine offers therapeutic opportunities by promoting tissue repair and modulating inflammation. Cellular orthobiologics such as mesenchymal stromal/stem cells (MSCs) show promise for treating osteoarthritis and tendon injuri...
Barreira AP, Moreira T, Silva R, Nunes L, Lioi A, Kraus E, Altheman V, Ribeiro M, Leite C, Silva A, Almeida F, Santos Junior G, Lessa D, Alves AL.Osteoarthritis (OA) is a degenerative joint disease that affects humans and animals worldwide. Its early diagnosis remains challenging due to subtle clinical signs and late radiographic changes. This study aimed to explore candidate biomarkers associated with spontaneous OA and to investigate their correlation with ultrasonographic scores to support early diagnosis. Clinical, radiographic, and ultrasonographic evaluations were performed on 52 equine metacarpophalangeal joints, with and without OA, allowing joint scoring and classification into osteoarthritis (OAG) and control groups. Synovial ...
Palomino Lago E, Roberts SJ, Orriss IR, Lumsden ES, Guest DJ.Bone is a dynamic tissue that is maintained through the co-ordination of bone resorption and bone formation. An imbalance of these processes can lead to bone disease. In vitro studies of osteoblasts can help to understand bone formation, but primary cells have a limited lifespan in culture. Herein, we report the successful generation of equine immortalized osteoblasts through the stable overexpression of human telomerase reverse transcriptase (hTERT) and Simian virus 40 (SV40) large T-antigen in osteoblasts isolated from trabecular bone taken from the third metacarpal of a two-year-old Thoroug...
Singer J, Chow L, Ammons D, Sabino I, Impastato R, Dow S, Pezzanite LM.Osteoarthritis (OA) is a aging-associated degenerative joint disease. The objective was to determine relative senescence gene expression in joints and leukocytes of OA horses toward considering senotherapeutics to manage OA. Unassigned: To define local (joint) and systemic (peripheral blood mononuclear cells [PBMCs]) senescence burden, synovial fluid cell single-cell RNA sequencing and PBMC mRNA sequencing datasets (n = 65 samples) were examined. Differential analyses were conducted using limma to compare OA versus control. A custom 3,043-gene senescence set curated from published metadata was...
Marković L, Vićić I, Lazarević Macanović M, Francuski Andrić J, Kovačević Filipović M, Radaković M.Working horses often develop distinct patterns of joint degeneration, yet research in this population remains limited. This study aimed to characterize degenerative changes in the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints of Serbian Mountain Horses using computed tomography (CT) and to explore their associations with synovial fluid (SF) biomarkers. A cross-sectional analysis was conducted on 32 MCP/MTP joints from eight clinically sound horses. Postmortem, joints underwent CT imaging, and SF samples were analyzed for viscosity, protein content, total nucleated cell count (...
Castanheira CIGD, Taylor S, Skiöldebrand E, Rubio-Martinez LM, Hackl M, Clegg PD, Peffers MJ.The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n = 4) and OA (n = 9) horses and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) was selected for validation in an independent coho...
van Veggel ECS, Cokelaere SM, Vanderperren K, Selberg KT, Rasmussen J, Bergman HJ, Vernooij JCM, Hoogelander B.To report low-field standing MRI findings and, when available, postmortem findings of 25 thoracic limbs with degenerative joint disease of the distal interphalangeal joint (DIPJ) characterized by narrowing of the joint space suggestive of cartilage loss. Unassigned: Medical records from September 2015 to July 2022 were reviewed for clinical history, signalment, MRI, and postmortem findings. The study retrospectively analyzed cases in which lameness was linked to DIPJ joint space narrowing using a partially nested comparative design. Width was measured at 4 DIPJ sites, as well as a ratio to the...
DI Stefano DA, Coccoluto L, Panina-Bordignon P, Brambilla E, Ruffini F, Murtaj V, Orlando F, Colombo M, Frigerio C, DI Bona A, Recupero D, Morroni M....Bone grafting is a surgical procedure that involves the use of bone tissue or bone substitutes to repair damaged bone. In dentistry and maxillofacial surgery, bone graft substitutes from various sources are commonly used. Given their critical role in clinical outcomes, it is essential to thoroughly investigate the biological and mechanical properties of these materials. Methods: In this in vitro study, we evaluated the biological properties of two equine-derived bone graft substitutes in comparison to β-tricalcium phosphate. The materials included one equine-derived graft containing hydrolyze...
Boado A, Pollard D, Dyson S.There are no studies that have investigated factors influencing the outcome of dressage horses with suspensory ligament (SL) branch injuries. The aim was to determine if age, breed, work level, injury severity, anatomical localisation of injury, number of injured branches, periligamentous fibrosis, persistence of power Doppler signal or coexistent osteoarthritis of a metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joint influenced the prognosis of 70 dressage horses. Outcome was defined as good (return to pre-injury level of work or higher), poor (return to a lower level of work) or ret...
Linde P, Kurihara J, Chow L, Williams ZJ, Hendrickson D, Bass L, Dow S, Pezzanite LM.Innate immune responses within the joint are now known to play a key role in osteoarthritis (OA) pathogenesis. However, comparatively little is known regarding the role of adaptive immune responses in OA, and whether they may be important for initiating and sustaining progressive low-level joint inflammation. Therefore, we evaluated spontaneous osteoarthritis in horses to investigate whether antibodies recognizing live joint cells (chondrocytes, synoviocytes) were present in blood or synovial fluid, and to identify possible cellular target antigens. We found that horses with advanced OA had an...
Beck C, Hitchens PL, Muir P, Whitton RC.Computed tomography (CT) is increasingly used for metacarpo/tarsophalangeal or fetlock joint (MC/TPJ) evaluation in Thoroughbred racehorses. CT features and lesion prevalence in competing Thoroughbreds are unknown. Objective: To identify standing CT features within the MC/TPJ of elite Thoroughbred staying racehorses. Methods: Retrospective cohort study. Methods: Computed tomography scans of the MC/TPJ were performed as part of pre-race screening for fracture risk and graded for CT features. Descriptive statistics and univariable logistic regression models were generated to investigate associat...
Peralta AG, Raeisimakiani P, Hayashi K, Mahal LK, Reesink HL.Post-traumatic osteoarthritis (PTOA) is a common sequela to joint injury in both humans and companion animal species such as horses and dogs. Despite the increasing prevalence of osteoarthritis (OA) in humans, investigation of glycosylation changes associated with OA remains in its infancy. Recent advances, such as lectin microarray analysis, now enable detailed glycan profiling in complex biofluids such as synovial fluid. Using lectin microarray technology, this study characterized glycosylation patterns in synovial fluid samples from healthy and OA-affected joints in horses, dogs, and humans...
Boado A, Pollard D, Lopez-Sanroman FJ, Dyson S.There is limited information regarding orthopaedic injuries in dressage horses. This study assessed the prevalence of injuries in a mixed referral and first opinion population of 272 horses training and competing in dressage, 238 of which were followed up one to five years after injury. Warmblood (55.8%) and Iberian (38.6%) breeds predominated. The median age was 8 years (interquartile range [IQR] 5,11; range 1,21). Horses were examined due to lameness (85.3%) or poor performance (14.7%). The median lameness grade was 2/5 (IQR 2,4; range 0,4). Forelimb lameness was more prevalent than hindlimb...
Samol MA, Barrett MF, Frisbie DD.Significant distal interphalangeal joint (DIPJ) pathology, particularly affecting soft tissue and articular cartilage, is often not identifiable on radiographs but can be accompanied by joint capsule enthesopathy on the middle phalanx (P2), which can be readily identified. Objective: To explore frequency and correlations between DIPJ capsule enthesopathy identified on magnetic resonance imaging (MRI) and radiographs and DIPJ articular cartilage abnormalities and other concurrent soft tissue or osseous pathology within the foot found on MRI. Methods: Retrospective descriptive case series. Metho...
Hartl B, Strohmayer C, Vali Y, Lyrakis M, Kneissl SM.Horses with hyoid bone disease may present with clinical symptoms such as exercise intolerance, resistance to ridden work, anorexia, or headshaking. This study aims to describe the computed tomographic (CT) signs and prevalence of hyoid disease and to evaluate their association with other CT changes of the head. Unassigned: In this study, four investigators conducted a retrospective analysis of their findings after reviewing the medical records of 200 horses that had undergone CT scans between 2009 and 2019. A total of 32 parameters were analyzed, and associations were evaluated between those ...
Mousquer MA, Paz CFR, Rafael LA, Wendt CG, Curcio BR, Souza RP, Santos IPOD, da Silva RB, Müller V, Nogueira CEW.Obesity is common in some horse breeds, raising concerns about health and performance. Criollo horses in morphological events often undergo intensive management promoting early adiposity. Objective: This study aimed (1) to assess morphometric traits, metabolic profile, hoof morphology, and tarsal joint alterations in Criollo horses participating in morphological trials; (2) to evaluate sex-related differences; and (3) the associations between morphometric measurements, hoof morphology, and tarsal osteoarthritis grades. Methods: Fifty-five horses (30 mares, 25 stallions) were evaluated for body...
Chaimbeul SF, Rodrigues NNP, Thurston DD, Scoggin KE, Janes J, Jacobs CA, MacLeod JN, Stone AV, Menarim BC.Synovitis resolution is critical for joint homeostasis and prevents the progression of osteoarthritis (OA). Treatments like NSAIDs and intra-articular corticosteroids relieve symptoms by blocking pro-inflammatory mediators, but also impair the production of pro-resolving mediators, contributing to the likelihood of chronic synovitis. PPARγ signaling is an essential mechanism of synovitis resolution, which is decreased in OA tissues. To evaluate the potential of PPARγ agonists to promote pro-resolving pathways, equine macrophages cultured in autologous, normal, or inflamed synovial fluid ( = ...
Sanchez-Arjona R, Lopez Cruz C, Hague BA, Jayawickrama J, Kamm JL.To evaluate the outcomes of diode laser-facilitated (DLF) ankylosis using different surgical techniques to treat distal tarsal osteoarthritis (OA) in horses. Methods: Retrospective cohort study. Methods: A total of 64 client-owned horses with distal tarsal OA treated with DLF ankylosis between 2011 and 2021 in a referral hospital were included. Methods: DLF ankylosis techniques included: intra-articular diode laser (L), diode laser with periarticular drilling (L + D) and diode laser with cuboidal bone fenestration (L + F). Horses requiring a second surgery formed a fourth group (T). Ou...
Bertone AL, Reinemeyer C, Tsaprailis G, Ragland D, Leise B.The use of micro-particulate allografts is rising, but knowledge about the protein characterization and biocompatibility of umbilical cord-derived allografts (UC) in vivo is limited. Methods: Proteomic analyses using mass spectrometry (MS) determined equine UC protein relative quantification and functions using total spectral counts (TSC). UC cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Three in vivo studies assessed recipient clinical and tissue biocompatibility in joints and ligaments. Results: Proteomics revealed 2645 annotated TSCs. Proteins of > 89 TSC we...
Chabronova A, Walters M, Regårdh S, Jacobsen S, Bundgaard L, Anderson JR, Peffers MJ.Osteoarthritis (OA) is a degenerative joint disease that greatly contributes to equine morbidity and poor welfare. Changes in cellular protein expression programs fuel the development and progression of OA. Small nucleolar RNAs (snoRNAs) are emerging as important regulators of OA (patho)biology. SnoRNAs are short non-coding RNAs that guide post-transcriptional modifications (PTMs) of ribosomal RNA (rRNA) nucleotides, which impact ribosome function and thus cellular protein expression programs. There is only very limited data on snoRNAs in equine OA. Unassigned: In this study, we induced OA in ...
Mathys RA, Schmitz TR, Geyer H, Borel N, Hilbe M, Ohlerth S, Bischofberger AS.This study described, assessed and correlated ultrasonographic, computed tomographic, and histological findings in the sacroiliac joints of adult Warmblood horse cadavers. In total, 25 joints from 15 horses were examined post-mortem using transrectal ultrasonography and helical computed tomography. Findings on computed tomography were graded in the caudal joint third (caudally) and for the entire joint as mild, moderate, or severe. In total, 11 joints from nine horses were evaluated histologically. All joints (100%) showed abnormalities on computed tomography, and 92% (23/25) displayed abnorma...
Berni P, Del Bue M, Conti V, Andreoli V, Ramoni R, Angelone M, Squassino GP, Bari E, Torre ML, Rinaldi M, Dotti S, Rossi R, Yusuf I, Mauri P....Most in vivo studies on MSC-secretome for osteoarthritis (OA) have relied on animal models, using products lacking pharmaceutical quality, not formulated for clinical use, and insufficiently characterized, limiting knowledge of its effectiveness. This study reports veterinary clinical trials on dogs and horses with spontaneous OA: in dogs (26 subjects), the trial is randomized, double-blinded, and controlled; in horses, 5 clinical cases were treated for safety assessment. Treatment consisted of hyaluronic acid with either lyosecretome - a freeze-dried, injectable MSC-secretome obtained through...
Contentin R, Jehl C, Commenchail K, Legendre F, Galéra P, Cassé F, Demoor M.Osteoarthritis (OA) affects millions of people globally, causing irreversible cartilage damage, chronic inflammation, and progressive joint dysfunction. Similarly, horses can develop OA spontaneously or due to their athletic careers, influenced by mechanical and biochemical factors. Current treatments primarily focus on symptom relief without promoting cartilage regeneration. In line with the 3Rs principles (refine, reduce, replace), the development of OA models is essential for advancing new therapeutic approaches against OA. In response to this need, the present study aimed to develop an m...
Hellige M, Geburek F.Diagnostic imaging is an important part of the diagnostic approach in equine spinal ataxia especially with the cervical spine being commonly involved. The spinal cord may be affected by a variety of conditions including cervical vertebral malformations, osteoarthritis of the articular process joints or less commonly neoplasia. Advanced imaging techniques such as myelography are more accurate in diagnosing spinal cord compression and may be performed under general anesthesia in neutral, flexed and extended positions of the cervical spine. The use of ultrasound is non-invasive and allows ultraso...
Boado A, Pollard D, Dyson S.There is limited information about the orthopaedic health of dressage horses. This study aimed to document the orthopaedic status, lesion distribution, and evolution of injuries in 70 horses undergoing a minimum of five in-depth orthopaedic assessments at six-months' intervals. Warmblood (70.0%) and Iberian (24.3%) breeds predominated. The median lameness grade at initial examination was 2/5 (interquartile range 2,2; range 0,3). Hypermetria (42.9%) or hypermetria and weakness (12.9%) were observed at the initial examination and did not change over time. Metacarpophalangeal/metatarsophalangeal ...
Lab on a chipMay 28, 2025
Volume 25, Issue 11 2795-2796 doi: 10.1039/d5lc90048d
Heidenberger J, Reihs EI, Strauss J, Frauenlob M, Gültekin S, Gerner I, Toegel S, Ertl P, Windhager R, Jenner F, Rothbauer M.Correction for 'The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models' by Johannes Heidenberger et al., Lab Chip, 2025, 25, 2256-2269, https://doi.org/10.1039/d4lc01078g.
Euppayo T, Siengdee P, Limlenglert P, Nganvongpanit K, Watanabe G, Kasashima Y, Arai K.The self-renewal capacity of chondrocytes in osteoarthritis (OA) joints is limited, and mesenchymal stem cells (MSCs) are crucial in disease treatment. This study established an OA model from equine bone marrow-derived mesenchymal stem cells (eBMSCs). The eBMSCs were cultured and differentiated into chondrocytes to generate cartilage pellets, which were induced for 7 d with inflammatory cytokines, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) to mimic OA conditions. Treated culture medium was collected to estimate enzyme activity (MMP-2, MMP-3, and MMP-9) using zymograph...
Gupta RC, Lall R, Srivastava A, Sinha A.Hyaluronic acid (also known as hyaluronan or hyaluronate) is naturally found in many tissues and fluids, but more abundantly in articular cartilage and synovial fluid (SF). Hyaluronic acid (HA) content varies widely in different joints and species. HA is a non-sulfated, naturally occurring non-protein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes. HA has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF. The concentration of HA and its ...
McCoy AM.Osteoarthritis (OA) is unquestionably one of the most important chronic health issues in humans, affecting millions of individuals and costing billions of dollars annually. Despite widespread awareness of this disease and its devastating impact, the pathogenesis of early OA is not completely understood, hampering the development of effective tools for early diagnosis and disease-modifying therapeutics. Most human tissue available for study is obtained at the time of joint replacement, when OA lesions are end stage and little can be concluded about the factors that played a role in disease deve...
Balazs EA, Denlinger JL.Viscosupplementation is a new medical concept that has as its therapeutic goal the restoration of rheological homeostasis in pathological structures such as osteoarthritic joints. When the normal viscoelasticity of a solid tissue compartment or the elastoviscosity of a liquid tissue compartment is decreased under pathological conditions, normal function and regenerative processes are impaired. By introducing viscosupplementary devices, the normal rheological state of such compartments is restored or augmented. These devices stay in the tissue compartment for various periods of time, depending ...
McIlwraith CW, Frisbie DD, Kawcak CE.Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative thera...
Frisbie DD, Ghivizzani SC, Robbins PD, Evans CH, McIlwraith CW.Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intra-articular overexpression of the equine interleukin-1 receptor antagonis...
Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW.The purpose of this study was the assessment of clinical, biochemical, and histologic effects of intraarticular administered adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. Osteoarthritis was induced arthroscopically in the middle carpal joint of all horses, the contralateral joint being sham-operated. All horses received treatment on Day 14. Eight horses received placebo treatment and eight horses received adipose-derived stromal vascular fraction in their osteoarthritis-affected joint. The final eight horses were treate...
McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A.Equine models of osteoarthritis (OA) have been used to investigate pathogenic pathways of OA and evaluate therapeutic candidates for naturally occurring equine OA which is a significant clinical disease in the horse. This review focuses on the macroscopic and microscopic criteria for assessing naturally occurring OA in the equine metacarpophalangeal joint as well as the osteochondral fragment-exercise model of OA in the equine middle carpal joint. Methods: A review was conducted of all published OA studies using horses and the most common macroscopic and microscopic scoring systems were summar...
Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW.To assess the clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum (ACS) in the treatment of experimentally induced osteoarthritis in horses. Methods: 16 horses. Methods: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. In 8 placebo- and 8 ACS-treated horses, 6 mL of PBS solution or 6 mL of ACS was injected into the osteoarthritis-affected joint on days 14, 21, 28, and 35, respectively; PBS solution was administered in the other sham-operated joints. Evaluations included clinical assessment of lamenes...
Sutton S, Clutterbuck A, Harris P, Gent T, Freeman S, Foster N, Barrett-Jolley R, Mobasheri A.Osteoarthritis (OA) is one of the most common and disabling chronic joint disorders affecting horses, dogs and humans. Synovial inflammation or synovitis is a frequently observed phenomenon in osteoarthritic joints and contributes to the pathogenesis of OA through formation of various catabolic and pro-inflammatory mediators altering the balance of cartilage matrix degradation and repair. Catabolic mediators produced by the inflamed synovium include pro-inflammatory cytokines, nitric oxide, prostaglandin E(2) and several neuropeptides, which further contribute to the pathogenesis of OA by incr...
Frisbie DD, Al-Sobayil F, Billinghurst RC, Kawcak CE, McIlwraith CW.To discriminate between changes in biomarkers with exercise compared to changes in biomarkers with osteoarthritis (OA) in exercising horses. Methods: Sixteen, 2-year-old horses were randomly assigned either to an exercise-alone (n=8) or OA-affected (also exercised) (n=8) group. All horses had both mid-carpal joints arthroscoped and OA induced in one mid-carpal joint in the OA-affected joints of OA-affected horses. Two weeks after surgery all horses commenced a strenuous exercise program on a high-speed treadmill. Clinical outcomes and synovial fluid and serum biomarkers, were evaluated weekly....
Goodrich LR, Nixon AJ.The medical treatment of osteoarthritis (OA) in the horse is one of the most utilized therapeutic regimens in the equine practice. It is important to understand the anatomy of synovial joints and the pathophysiology of the disease process to treat OA adequately. Once a thorough understanding of the disease process is comprehended the proper combination of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and chondroprotectants can be used to treat the disease and inhibit further progression of degenerative changes to the cartilage surface. Th...
Stewart HL, Kawcak CE.Subchondral bone plays a critical role in the pathogenesis of osteochondral disease across veterinary species. The subchondral bone is highly adaptable, with the ability to model and remodel in response to loading stresses experienced by the joint. Repetitive stress injuries within the joint can result in primary or secondary pathologic lesions within the subchondral bone, which have been recognized to contribute to the development and progression of osteoarthritis. Recent advances in diagnostic imaging, particularly volumetric imaging modalities have facilitated earlier identification of subc...
Malda J, Benders KE, Klein TJ, de Grauw JC, Kik MJ, Hutmacher DW, Saris DB, van Weeren PR, Dhert WJ.Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic ap...
Bi X, Yang X, Bostrom MP, Camacho NP.Significant complications in the management of osteoarthritis (OA) are the inability to identify early cartilage changes during the development of the disease, and the lack of techniques to evaluate the tissue response to therapeutic and tissue engineering interventions. In recent studies several spectroscopic parameters have been elucidated by Fourier transform infrared imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and compositional changes in human cartilage with progressively severe OA, and in repair cartilage from animal models. FT-IRIS permits evaluation of early-stag...
Bi X, Li G, Doty SB, Camacho NP.The orientation of collagen molecules is an important determinant of their functionality in connective tissues. The objective of the current study is to establish a method to determine the alignment of collagen molecules in histological sections of cartilage by polarized Fourier transform infrared imaging spectroscopy (FT-IRIS), a method based on molecular vibrations. Methods: Polarized FT-IRIS data obtained from highly oriented tendon collagen were utilized to calibrate the derived spectral parameters. The ratio of the integrated areas of the collagen amide I/II absorbances was used as an ind...
Frisbie DD, Lu Y, Kawcak CE, DiCarlo EF, Binette F, McIlwraith CW.Current autologous chondrocyte implantation (ACI) techniques require 2 surgical procedures: 1 for cell harvest and 1 for reimplantation of cultured cells. A 1-step procedure is more desirable. Objective: A 1-step surgical procedure using autologous cartilage fragments on a polydioxanone scaffold, or CAIS (cartilage autograft implantation system), in a clinically relevant defect (15-mm diameter) within equine femoral trochlea was compared with a 2-step ACI technique as well as with empty defects and defects with polydioxanone foam scaffolds alone. Methods: Controlled laboratory study. Methods: ...
Peffers M, Liu X, Clegg P.Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. Methods: RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopicall...
Rosser J, Bachmann B, Jordan C, Ribitsch I, Haltmayer E, Gueltekin S, Junttila S, Galik B, Gyenesei A, Haddadi B, Harasek M, Egerbacher M, Ertl P....In this work, we describe a microfluidic three-dimensional (3D) chondrocyte culture mimicking in vivo articular chondrocyte morphology, cell distribution, metabolism, and gene expression. This has been accomplished by establishing a physiologic nutrient diffusion gradient across the simulated matrix, while geometric design constraints of the microchambers drive native-like cellular behavior. Primary equine chondrocytes remained viable for the extended culture time of 3 weeks and maintained the low metabolic activity and high Sox9, aggrecan, and Col2 expression typical of articular chondrocytes...
Rivas F, Zahid OK, Reesink HL, Peal BT, Nixon AJ, DeAngelis PL, Skardal A, Rahbar E, Hall AR.Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA w...
Huser CA, Davies ME.Chondrocyte apoptosis is an important factor in the progression of osteoarthritis. This study aimed to elucidate the mechanisms involved upstream of caspase 9 activation and, in particular, calcium signaling and mitochondrial depolarization. Methods: Articular cartilage explants obtained from healthy horses were subjected to a single impact load (500-gm weight dropped from a height of 50 mm) and cultured in vitro for up to 48 hours. Chondrocyte death was quantified by the TUNEL method. Release of proteoglycans was determined by the dimethylmethylene blue assay. Weight change was measured, and ...
Bertone AL, Ishihara A, Zekas LJ, Wellman ML, Lewis KB, Schwarze RA, Barnaba AR, Schmall ML, Kanter PM, Genovese RL.To evaluate intra-articular autologous protein solution (APS) for the treatment of osteoarthritis in horses. Animals-40 client-owned horses with naturally occuring osteoarthritis. Methods: APS was generated from a dual-device system that concentrated plasma and WBC proteins and enriched platelet growth factors. Horses were randomly assigned to receive an intra-articular injection of 5 mL of saline (0.9% NaCl) solution (n = 20) or APS (20), exercised on a treadmill, and evaluated on the basis of lameness grades, kinetic gait analysis, joint circumference, and range of motion for 14 days. Horses...
Bertuglia A, Lacourt M, Girard C, Beauchamp G, Richard H, Laverty S.The role of osteoclasts in osteochondral degeneration in osteoarthritis (OA) has rarely been investigated in spontaneous disease or animal models of OA. Objective: The objectives of the current study were to investigate osteoclast density and location in post-traumatic OA (PTOA) and control specimens from racehorses. Methods: Cores were harvested from a site in the equine third carpal bone, that undergoes repetitive, high intensity loading. Histological and immunohistochemical (Cathepsin K and Receptor-activator of Nuclear Factor kappa-β ligand (RANKL)) stained sections were scored (global an...
Kamm JL, Nixon AJ, Witte TH.Understanding the expression of catabolic and anabolic genes during osteoarthritis progression should help to identify the major mediators of the disease. Objective: To compare the cytokine and anabolic marker concentrations in synovium, synovial fluid and cartilage between normal and osteoarthritic joints. Methods: Carpi from horses age 2-11 years were used. Tissues were harvested at the time of surgery or euthanasia, and RNA was isolated for RT-PCR analysis. Tumour necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), aggrecanase 1 (ADAMTS-4), aggrecanase 2 (ADAMTS-5), matrix metallopro...
Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P.Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappaB-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalan...
Barrachina L, Remacha AR, Romero A, Vitoria A, Albareda J, Prades M, Roca M, Zaragoza P, Vázquez FJ, Rodellar C.This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months tim...
Strauss EJ, Goodrich LR, Chen CT, Hidaka C, Nixon AJ.Chondral defects may lead to degradative changes in the surrounding cartilage, predisposing patients to developing osteoarthritis. Objective: To quantify changes in the biomechanical and biochemical properties of the articular cartilage adjacent to chondral defects after experimental defect repair. Methods: Controlled laboratory study. Methods: Specimens were harvested from tissue within (lesion), immediately adjacent to, and at a distance from (remote area) a full-thickness cartilage defect 8 months after cartilage repair with genetically modified chondrocytes expressing insulin-like growth f...
Garbin LC, Olver CS.Autologous platelet-rich plasma (PRP) is a biological preparation made from the patient's own plasma that contains a platelet concentration above the whole blood baseline. Owing to the release of growth factors and other cytokines after degranulation, platelets have a central role in inflammation and in different stages of the healing process. For this reason, PRP-derived products have been used to enhance healing of musculoskeletal injuries and modulate progression of inflammatory processes, including osteoarthritis (OA). Osteoarthritis is one of the main causes of musculoskeletal disabilitie...
Haupt JL, Frisbie DD, McIlwraith CW, Robbins PD, Ghivizzani S, Evans CH, Nixon AJ.This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (1...
Frisbie DD, Kawcak CE, Trotter GW, Powers BE, Walton RM, McIlwraith CW.The objective of this study was to determine the effects of intra-articularly administered triamcinolone acetonide (TA) in exercised equine athletes with carpal osteochondral fragmentation. Eighteen horses were randomly assigned to each of 3 groups. An osteochondral chip fragment was created in one randomly chosen intercarpal joint of each horse. Both intercarpal joints in the placebo control group (CNT) horses were injected with intra-articular administration (IA) of polyionic fluid. Both joints in the TA control group (TA CNT) horses were treated with 12 mg of TA in the intercarpal joint wit...
Steinbusch MM, Fang Y, Milner PI, Clegg PD, Young DA, Welting TJ, Peffers MJ.The development of effective treatments for the age-related disease osteoarthritis and the ability to predict disease progression has been hampered by the lack of biomarkers able to demonstrate the course of the disease. Profiling the expression patterns of small nucleolar RNAs (snoRNAs) in joint ageing and OA may provide diagnostic biomarkers and therapeutic targets. This study determined expression patterns of snoRNAs in joint ageing and OA and examined them as potential biomarkers. Using SnoRNASeq and real-time quantitative PCR (qRT-PCR) we demonstrate snoRNA expression levels in murine age...
