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.
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...
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...
Rinnovati R, Spadari A, Malpighi A, Meistro F, Ralletti MV, Marcucci E, Tarasconi MA, Chiatto RL, Tommasa SD.Numerous treatment strategies have been proposed to manage osteoarthritis (OA) in sport horses. Carboxymethylcellulose (CMC), is used in veterinary medicine for various purposes. Objective: This study aimed to assess the efficacy of a CMC hydrogel in reducing clinical lameness in horses with OA affecting joint. The hypothesis was that intra-articular CMC would produce a sustained reduction in lameness compared to a control treatment. Methods: Thirty client-owned horses diagnosed with OA-related lameness in the metacarpophalangeal joint were enrolled. Horses were randomly assigned to two groups...
Pluim M, Frippiat T.Polyacrylamide gel is increasingly used in equine veterinary medicine for osteoarthritis and other joint disorders. This study aimed to document the indications, treatment protocols, rehabilitation plans, outcomes, and satisfaction with intra-articular polyacrylamide gel in horses, as reported by equine veterinarians. An online questionnaire was distributed to practitioners through the European and American Colleges of Veterinary Sports Medicine and Rehabilitation mailing lists, social media, and direct contact. Of 197 respondents, 160 completed the survey, forming the basis for the descriptiv...
Luque RM, Henderson B, McCorkell TC, Alizadeh AH, Russell KA, Koch TG, Koenig J.Mesenchymal stromal cells (MSCs) are widely used to treat osteoarthritis (OA). Optimising dose, timing, and safety while comparing efficacy with standard therapies like hyaluronic acid (HA) is essential for their standardisation. Objective: To assess the safety and efficacy of equine umbilical cord-derived (eCB) MSCs in client-owned horses with fetlock or carpus OA. Methods: Prospective single-blinded randomised clinical study. Methods: Horses diagnosed with fetlock or carpus OA via intra-articular (IA) anaesthesia were randomly assigned to receive either 10 or 20 million eCB-MSCs in HA or 3â€...
Beck AA, Paz LB, Frank MI, Pereira RCF, De La Côrte FD.To evaluate the effect of IA injections of botulinum toxin type A (BoNT-A) in horses with chronic, naturally occurring distal tarsal osteoarthritis. Unassigned: 9 horses were selected after physical and radiographic assessments. Horses also underwent an objective lameness examination and were included if they had a hindlimb impact lameness (Pmin ≥ 3 mm), which positively responded (≥ 50%) to the tarsometatarsal and centrodistal joints' anesthetic block. Horses randomly received an intra-articular injection of BoNT-A or an equivalent volume of saline solution. Horses were reevaluated at pos...
Secor EJ, Womack SJ, Ysebaert MP, Colville MJ, Reesink HL.Synovial fluid (SF) is an ideal sentinel fluid for osteoarthritis (OA) diagnosis and prognostication due to its critical homeostatic role, proximity to articular tissues and immune cell composition. Untargeted proteomics enable identification of soluble markers for diagnostic and therapeutic applications while minimising bias. Objective: To use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to define the SF proteome in horses with and without carpal OA. The goal was to identify differentially regulated proteins in mild-moderate carpal joint disease compared with healthy joints. Meth...
Buzelato Carli I, Fielding L.Many horses receive firocoxib over multiple years, and studies evaluating hematologic and biochemical values in these animals are lacking. Objective: To describe the hematologic and biochemical values of horses receiving long-term firocoxib. Methods: A total of 79 horses receiving long-term firocoxib and 153 horses not receiving long-term firocoxib and not presenting for a specific medical problem. Methods: Retrospective study comparing horses receiving firocoxib (F group) and no firocoxib (NF group). Signalment, hematologic, and biochemical values were compared between the two groups. Simple ...
Klymiuk MC, Speer J, Marco I, Elashry MI, Heimann M, Wenisch S, Arnhold S.Osteoarthritis (OA) is a common and incurable disease in humans and animals. To gain a better understanding of the pathogenesis and identify potential treatments, miRNAs will be extracted and analysed from extracellular vesicles (EVs) of equine adipose derived mesenchymal stem cells (AdMSCs). Methods: For this purpose we cultivated and pretreated AdMSCs under different conditions: interleukin 1β, shock wave, chondrogenic differentiation, chondrogenic differentiation under hypoxia, or after senescence. After treatment, EVs were harvested from the cell culture supernatants. Next-generation sequ...
Heidenberger J, Reihs EI, Strauss J, Frauenlob M, Gültekin S, Gerner I, Tögel S, Ertl P, Windhager R, Jenner F, Rothbauer M.Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, chronic inflammation, and progressive joint dysfunction. Despite rising incidences driven by ageing and increasing obesity, potent treatments remain elusive, exacerbating the socioeconomic burden. OA pathogenesis involves an imbalance in extracellular matrix (ECM) turnover, mediated by inflammatory cytokines and matrix-degrading enzymes, leading to oxidative stress, chondrocyte apoptosis, and ECM degradation. Additionally, synovial inflammation (synovitis) plays a critical role in disease pro...
Turek B, Pawlikowski M, Jankowski K, Borowska M, Skierbiszewska K, Jasiński T, Domino M.In veterinary medicine, conventional radiography is the first-choice method for most diagnostic imaging applications in both small animal and equine practice. One direction in its development is the integration of bone density evaluation and artificial intelligence-assisted clinical decision-making, which is expected to enhance and streamline veterinarians' daily practices. One such decision-support method is k-means clustering, a machine learning and data mining technique that can be used clinically to classify radiographic signs into healthy or affected clusters. The study aims to investigat...
Perrone G, Giampaoli C, Smirnoff AL, Ochoa A, Pareja R, De Simone E.Osteoarthritis (OA) is the most common pathology in sport horses, presenting a chronic and recurrent course. Traditional anti-inflammatory treatments provide only temporary clinical improvement and pain relief; however, they have been associated with metabolic disorders in articular cartilage in the medium term. In this study, we generated a llama polyclonal antibody against equine TNF-α, which was used for intra-articular treatment in horses with OA. Treatment effects were assessed through clinical examination and the determination of inflammatory parameters (MMP-2, MMP-9, LDH, and GAGs) in ...
Luedke LK, Seabaugh KA, Cooper BG, Snyder BD, Wimmer MA, McIlwraith CW, Barrett MF, Kawcak CE, Grinstaff MW, Goodrich LR.Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated j...
Jasiński T, Turek B, Kaczorowski M, Brehm W, Skierbiszewska K, Domino M.The temporomandibular joint (TMJ) is a unique joint that enables mandibular movement. Temporomandibular diseases (TMDs) impair joint function, leading to more or less specific clinical signs. Objective: To compile and disseminate clinical data and research findings from existing publications on equine TMD. Methods: Systematic review. Methods: Following PRISMA 2020 guidelines, literature searches were conducted in PUBMED, Scopus, and Web of Knowledge. The inclusion criteria covered case reports and research articles on equine TMDs. The selected records were grouped considering septic TMJ arthri...
Palomino Lago E, Ross AKC, McClellan A, Guest DJ.Bone fractures are a significant problem in Thoroughbred racehorses. The risk of fracture is influenced by both genetic and environmental factors. To determine the biological processes that are affected in genetically susceptible horses, we utilised polygenic risk scoring to establish induced pluripotent stem cells (iPSCs) from horses at high and low genetic risk. RNA-sequencing on iPSC-derived osteoblasts revealed 112 genes that were significantly differentially expressed. Forty-three of these genes have known roles in bone, 27 are not yet annotated in the equine genome and 42 currently have ...
Walters M, Skovgaard K, Heegaard PMH, Fang Y, Kharaz YA, Bundgaard L, Skovgaard LT, Jensen HE, Andersen PH, Peffers MJ, Jacobsen S.MicroRNAs, a class of small noncoding RNAs, serve as post-transcriptional regulators of gene expression and are present in a stable and quantifiable form in biological fluids. MicroRNAs may influence intra-articular responses and the course of disease, but very little is known about their temporal changes in osteoarthritis. Objective: To identify miRNAs and characterise the temporal changes in their abundance in SF from horses with experimentally induced osteoarthritis. We hypothesised that the abundance of miRNA would change during disease progression. Methods: In vivo experiments. Methods: R...
Costa GL, Tabbì M, Bruschetta G, Spadola F, Leonardi F, Bruno F, Iannelli NM, Licata P, Macrì F, Passino ES, Macrì D, Interlandi C.The study aimed to evaluate the analgesic efficacy of tapentadol in horses, by determining plasma serotonin concentration and adrenocortical response, as biomarkers of pain stress in chronic joint disorders. Thirty-six horses (20 females and 16 males) were divided into three groups of 12 subjects each: group A, osteoarthritis (OA), grade 3-4 lameness; group B, OA, grade 5 lameness; and group C, no OA, no lameness, were enrolled. The orthopedic examination included flexion tests, and radiological and ultrasound examinations. The degree of lameness has been estimated from 0 to 5 according to the...
Guidoni K, Chiaradia E, Pepe M, Di Meo A, Tognoloni A, Seccaroni M, Beccati F.Intra-articular corticosteroids, such as triamcinolone acetonide (TA), help reduce pain related to osteoarthritis (OA), but they may impair cartilage metabolism. In contrast, platelet-rich plasma (PRP) therapy, a regenerative therapy, has shown potential to promote healing and regeneration of articular cartilage. This study investigates the effects of combining PRP with TA to treat osteoarthritis in racehorses. The study proposes that PRP injection following TA treatment could reduce side effects and improve treatment outcomes. Firstly, in the in vitro study, chondrocytes were exposed to diffe...
Chow L, Kawahisa-Piquini G, Bass L, Hendrickson D, Patel A, Rockow M, Dow S, Pezzanite LM.Osteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immun...
Elkhenany HA, Linardi RL, Ortved KF.Osteoarthritis (OA) remains a challenging joint disorder necessitating effective anti-inflammatory interventions. In this study, our primary objective was to establish an in vitro protocol that replicates the clinical investigation of anti-inflammatory drugs intended for OA management. Focusing on recombinant IL-10 (r.IL-10) as a potential anti-inflammatory treatment, we designed and implemented two distinct protocols to evaluate the efficacy of r.IL-10 in modulating chondrocyte and synoviocyte inflammation.The experimental design involved sequential stimulation with IL-1β and TNF-α for 24 ...
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, 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...
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, 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...
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...
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 ...
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...
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...
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...
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...
Lacourt M, Gao C, Li A, Girard C, Beauchamp G, Henderson JE, Laverty S.To correlate degenerative changes in cartilage and subchondral bone in the third carpal bone (C3) of Standardbred racehorses with naturally occurring repetitive trauma-induced osteoarthritis. Methods: Fifteen C3, collected from Standardbred horses postmortem, were assessed for cartilage lesions by visual inspection and divided into Control (CO), Early Osteoarthritis (EOA) and Advanced Osteoarthritis (AOA) groups. Two osteochondral cores were harvested from corresponding dorsal sites on each bone and scanned with a micro-computed tomography (CT) instrument. 2D images were assembled into 3D reco...
Neundorf RH, Lowerison MB, Cruz AM, Thomason JJ, McEwen BJ, Hurtig MB.To determine the prevalence and severity of osteoarthritis in the metacarpophalangeal joints of Thoroughbred racehorses via development and validation of a quantitative macroscopic evaluation system. Methods: Metacarpophalangeal joints from 50 Thoroughbred racehorses. Methods: Joints were collected from horses that died or were euthanized within 60 days of racing. Metacarpophalangeal joints were assessed for osteoarthritic degeneration by use of macroscopic and histologic scoring systems, polarized light microscopy, and cartilage biochemical analysis. The global macroscopic score for the entir...
Ross TN, Kisiday JD, Hess T, McIlwraith CW.To compare two transient models of synovitis-osteoarthritis (OA) in horses by characterizing biological changes in synovial fluid and joint tissue. Methods: Twelve skeletally mature mares were utilized in a block design. Synovitis was induced by an intra-articular injection of 100 ng recombinant equine interleukin 1 beta (reIL-1β) or 0.5 ng lipopolysaccharide (LPS) into a middle carpal joint in 1 ml volumes. One ml of saline was injected into the contra-lateral control joint. Lameness evaluations were conducted through post-injection hour (PIH) 8 (at which time arthroscopic removal of syno...
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...
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...
van der Kraan PM.Osteoarthritis (OA) is the most common joint disease but an effective pharmacological therapy has not been developed yet. To identify targets for treatment and ways to interfere with OA development and progression both spontaneous and induced OA models are still needed. In this narrative review it is discussed what variables can be identified that lead to variation in OAÂ animal model studies. Literature was screened (Pubmed) with the following terms; OA animal models in combination with species, age, strain, gender/sex, housing, diet, fighting, circadian rhythm, transgenic. Relevant articles ...
Radtke CL, Nino-Fong R, Esparza Gonzalez BP, Stryhn H, McDï¿® LA.To characterize equine muscle tissue- and periosteal tissue-derived cells as mesenchymal stem cells (MSCs) and assess their proliferation capacity and osteogenic potential in comparison with bone marrow- and adipose tissue-derived MSCs. Methods: Tissues from 10 equine cadavers. Methods: Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and adipose tissue from the left subcutaneous region. Mesenchymal stem cells were characterized on the basis of morphology, ad...
