Synovial fluid is a viscous, lubricating liquid found within the joint cavities of horses. It serves to reduce friction between the articular cartilage of synovial joints during movement. Composed primarily of hyaluronic acid and lubricin, synovial fluid also contains proteins, electrolytes, and cells. Its composition can change in response to joint disease or injury, making it a subject of interest in veterinary diagnostics. Analyzing synovial fluid can provide insights into joint health, inflammation, and the presence of infections. This page compiles peer-reviewed research studies and scholarly articles that explore the composition, function, and diagnostic applications of synovial fluid in equine medicine.
Fasanello DC, Su J, Deng S, Yin R, Colville MJ, Berenson JM, Kelly CM, Freer H, Rollins A, Wagner B, Rivas F, Hall AR, Rahbar E, DeAngelis PL....TNF-α-stimulated gene 6 (TSG-6) protein, a TNF-α-responsive hyaladherin, possesses enzymatic activity that can catalyze covalent crosslinks of the polysaccharide hyaluronic acid (HA) to another protein to form heavy chain-hyaluronic acid (HC-HA) complexes in pathological conditions such as osteoarthritis (OA). Here, we examined HA synthase and inflammatory gene expression; synovial fluid HA, TNF-α, and viscosity; and TSG-6-mediated HC-HA complex formation in an equine OA model. The objectives of this study were to (1) evaluate the TNF-α-TSG-6-HC-HA signaling pathway across multiple joint t...
Tucker L, Trumble TN, Groschen D, Dobbs E, Baldo CF, Wendt-Hornickle E, Guedes AGP.Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation. Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 μg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed...
Temple-Wong MM, Raleigh AR, Frisbie DD, Sah RL, McIlwraith CW.To assess whether the combination of hyaluronan, sodium chondroitin sulfate, and -acetyl-d-glucosamine (HCSG) lubricates articular cartilage in vitro and modulates joint lubrication in vivo. Methods: 16 healthy adult horses. Methods: The effects of HCSG injections on SF lubricant properties and joint health, immediately after injury and 2 weeks later, were analyzed by use an equine osteochondral fracture model of post-traumatic osteoarthritis (OA). Middle carpal joints of adult horses were randomly assigned to 1 of 4 surgical treatment groups as follows: normal nonsurgical group (n = 8), norma...
Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G.The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten ( = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9...
Fülber J, Agreste FR, Seidel SRT, Sotelo EDP, Barbosa ÂP, Michelacci YM, Baccarin RYA.Mesenchymal stem cells (MSCs) represent a promising therapy for the treatment of equine joint diseases, studied due to their possible immunomodulatory characteristics and regenerative capacity. However, the source of most suitable MSCs for producing cartilage for regenerative processes in conjunction with biomaterials for an enhanced function is yet to be established. Objective: To compare the chondrogenicity of MSCs derived from synovial fluid, bone marrow, and adipose tissue of horses, using the aggrecan synthesis. Methods: MSCs from ten horses were cultured, phenotypic characterization was ...
Krause DM, Pezzanite LM, Griffenhagen GM, Hendrickson DA.Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed. Objective: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings. Methods: Retrospective cohort study. Methods: Records from the Colorado State University were evaluated (2014-2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising se...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Haralambus R, Florczyk A, Sigl E, Gültekin S, Vogl C, Brandt S, Schnierer M, Gamerith C, Jenner F.Synovial sepsis is a commonly occurring, potentially career-ending or even life-threatening orthopaedic emergency. Diagnosis of synovial sepsis is currently primarily based on synovial fluid analysis, which often leaves diagnostic ambiguity due to overlap of clinicopathological parameters between septic and aseptic inflammatory synovitis. Objective: To evaluate the reliability of lysozyme (LYS), myeloperoxidase (MPO) and elastase (ELT) as biomarkers for synovial sepsis in horses using a photometric assay to measure increased enzyme activity. Methods: Prospective, single-blinded, analytical, cl...
Pezzanite L, Chow L, Hendrickson D, Gustafson DL, Russell Moore A, Stoneback J, Griffenhagen GM, Piquini G, Phillips J, Lunghofer P, Dow S....Septic arthritis causes significant morbidity and mortality in veterinary and human clinical practice and is increasingly complicated by multidrug-resistant infections. Intra-articular (IA) antibiotic administration achieves high local drug concentrations but is considered off-label usage, and appropriate doses have not been defined. Using an equine joint model, we investigated the effects of amikacin injected at three different doses (500, 125, and 31.25 mg) on the immune and cartilage responses in tibiotarsal joints. Synovial fluid (SF) was sampled at multiple time points over 24 h, the cell...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Ahmad WA, Prince H, Kelmer G. The aim of this study was to determine the concentration of metronidazole in the distal interphalangeal joint (DIPJ) of the thoracic limb after administering metronidazole to standing horses by intravenous regional limb perfusion (IVRLP). Methods: Eleven healthy horses had a wide rubber tourniquet applied to the proximal aspect of the antebrachium for 0.5 hours and 500 mg of metronidazole diluted in physiologic saline solution to a total volume of 108 mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 ...
Watkins A, Fasanello D, Stefanovski D, Schurer S, Caracappa K, D'Agostino A, Costello E, Freer H, Rollins A, Read C, Su J, Colville M, Paszek M....Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hya...
Della Tommasa S, Winter K, Seeger J, Spitzbarth I, Brehm W, Troillet A.Horses are a widely accepted model for osteoarthritis (OA) research. Synovial tissue sampling is commonly used in studies to evaluate and grade the progress of OA or to assess treatment effects. Synovial explants play an important role in ex-vivo studies, increasingly replacing the use of living animals. To understand histomorphological changes in the process of joint-related diseases such as OA, detailed information about histomorphometric parameters of unaffected synovial villi is necessary. The objective of the present study was to evaluate the mean width of the intimal synovial lining and ...
Christmann U, Hancock CL, Poole CM, Emery AL, Poovey JR, Hagg C, Mattson EA, Scarborough JJ, Christopher JS, Dixon AT, Craney DJ, Wood PL.Horses with asthma or osteoarthritis frequently receive ω-3 fatty acid supplements. Docosahexaenoic (DHA; 22:6) and eicosapentaenoic (EPA; 20:5) acids are essential ω-3 fatty acid precursors of anti-inflammatory mediators and components of structural glycerophospholipids (GPL) that act as reservoirs of these fatty acids. Analysis of the incorporation of dietary DHA + EPA into GPL pools in different body compartments has not been undertaken in horses. We undertook a detailed study of dietary supplementation with DHA + EPA in horses and monitored incorporation into DHA- and EPA-contain...
Kosinska MK, Eichner G, Schmitz G, Liebisch G, Steinmeyer J.The current limitations in evaluating synovial fluid (SF) components in health and disease and between species are due in part to the lack of data on normal SF, because of low availability of SF from healthy articular joints. Our study aimed to quantify species-dependent differences in phospholipid (PL) profiles of normal knee SF obtained from equine and human donors. Knee SF was obtained during autopsy by arthrocentesis from 15 and 13 joint-healthy human and equine donors, respectively. PL species extracted from SF were quantitated by mass spectrometry whereas ELISA determined apolipoprotein ...
Noordwijk KJ, Qin R, Diaz-Rubio ME, Zhang S, Su J, Mahal LK, Reesink HL.Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial fluid biomarkers could contribute to the diagnosis and understanding of osteoarthritis (OA) pathophysiology. Objective: The aim of this study was to identify differentially expressed metabolic and glycosylation pathways in synovial fluid from healthy horses and horses with naturally occurring carpal OA. Methods: Cross-sectional, in vivo metabolomics and glycomics study. Methods: In cohort 1, carpal synovial fluid (n = 12 horses...
Conrado FO, Beatty SSK.Fluid analysis is an important part of the diagnostic work-up of equine patients presenting with disorders of the nervous system, musculoskeletal system, and abdominal cavity. Proper specimen handling and processing are paramount for complete and accurate interpretation of fluid samples. Normal cerebrospinal fluid is a low-cellularity, low-protein fluid requiring specific sample handling to ensure accurate results. Joint and abdominal fluid analyses are completed in practice or submitted for analysis to a reference laboratory. This article discusses fluid sample handling and processing conside...
Frydendal C, Nielsen KB, Berg LC, van Galen G, Adler DMT, Andreassen SM, Jacobsen S.To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. Methods: Experimental studies and retrospective clinical study. Methods: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivac...
Te Moller NCR, Mohammadi A, Plomp S, Serra Bragança FM, Beukers M, Pouran B, Afara IO, Nippolainen E, Mäkelä JTA, Korhonen RK, Töyräs J....This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8-week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait...
Kilcoyne I, Nieto JE, Galuppo LD, Dechant JE.To determine the median time to maximum concentration (t) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. Methods: 7 healthy adult horses. Methods: With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrur...
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...
Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ.Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. Objective: To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation. Methods: Randomised controlled experimental study. Methods: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone...
Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE.Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared wi...
Ogden NKE, Cullen MD, Stack JD.Accuracy of intrasynovial injections can be challenging to assess in a clinical setting in horses. Contrast-enhanced ultrasonography (CEUS) using injectate agitated with air has been used to determine the success rates of synovial injections in human rheumatology. Objective: To assess the diagnostic sensitivity and specificity of CEUS and to describe its clinical use. Methods: Cadaveric study followed by a prospective descriptive observational study. Methods: Part 1: CEUS was performed following injection of agitated methylene-blue solution targeting 13 different anatomical synovial structures...
Brown KA, Davidson EJ, Johnson AL, Wulster KB, Ortved K.Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. Objective: Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multipl...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Kendall A, Nyström S, Ekman S, Hultén LM, Lindahl A, Hansson E, Skiöldebrand E.Nerve growth factor (NGF) is a neurotrophin with many functions. In humans, it is involved in inflammation, nerve growth, apoptosis and pain signalling. Increased concentrations of NGF in synovial fluid has been shown in humans and dogs with osteoarthritis. Despite osteoarthritis being a common problem in horses, no studies have previously been published on NGF in the equine joint. The aim of this study was to quantify NGF in equine synovial fluid from healthy joints, acutely inflamed septic joints and joints with structural changes associated with osteoarthritis. A secondary aim was to identi...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Pritchard A, Nielsen BD, Robison C, Manfredi JM.As osteoarthritis is a major cause of lameness in horses in the United States, improving collagen health prior to onset and increasing collagen turnover within affected joints could improve health- and welfare-related outcomes. Through its positive effects on bone mineral content and density and its role in increasing collagen synthesis, silicon (Si) may slow the development and progression of osteoarthritis, thereby reducing lameness. This study evaluated the hypothesis that Si supplementation would increase cartilage turnover through increased collagen degradation and formation markers, as w...
Elzer EJ, Wulster KB, Richardson DW, Ortved KF.A 15-year-old Thoroughbred gelding was presented for investigation of fever, right temporomandibular region swelling, and progressive pain when opening the mouth. Right temporomandibular joint (TMJ) sepsis was diagnosed based on synovial fluid analysis, sonographic imaging, and standing robotic cone-beam computed tomography. Concurrent otitis media and temporohyoid osteoarthropathy (THO) were also noted. The horse was treated with arthroscopic debridement and lavage during standing sedation followed by local and systemic antimicrobial therapy. There were no complications associated with the su...
Yoshimura S, Koziy RV, Dickinson R, Moshynskyy I, McKenzie JA, Simko E, Bracamonte JL.While serum amyloid A (SAA) has been investigated as a potential marker for septic arthritis in horses, no study has reported on whether SAA can be used to detect eradication of joint infection. Therefore, the objective of this study was to investigate whether the eradication of joint infection in experimentally induced septic arthritis in horses can be detected using serum and synovial fluid SAA. A total of 17 horses were randomly assigned to 3 groups. A middle carpal joint of each horse was injected with saline (control group, = 3), lipopolysaccharide (LPS) (nonseptic synovitis group, = 6)...
Anderson JR, Johnson E, Jenkins R, Jacobsen S, Green D, Walters M, Bundgaard L, Hausmans BAC, van den Akker G, Welting TJM, Chabronova A, Kharaz YA....Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. ...
Iaconisi GN, Gallo N, Caforio L, Ricci V, Fiermonte G, Della Tommasa S, Bernetti A, Dolce V, Farì G, Capobianco L.Hyaluronic acid (HA) naturally occurs as a biopolymer in the human body, primarily in connective tissues like joints and skin. Functioning as a vital element of synovial fluid, it lubricates joints, facilitating fluid movement and diminishing bone friction to protect articular well-being. Its distinctive attributes encompass notable viscosity and water retention capacities, ensuring flexibility and absorbing shock during motion. Furthermore, HA has gained significant attention for its potential benefits in various medical applications, including rehabilitation. Ongoing research explores its pr...
Schwarz IM, Hills BA.Previous studies have shown that synovial surfactant could have beneficial roles in the joint, especially as a very effective boundary lubricant capable of high load bearing. This study is aimed at further characterization and identification of the source. Known to be an important minor component of pulmonary surfactant, proteolipid has now been detected in appreciable quantities in bovine synovial fluid and bound to the articular surface. Using standard procedures to separate it from the major component [surface-active phospholipid (SAPL)] by column chromatography, proteolipid: phospholipid r...
DePuy T, Howard R, Keegan K, Wilson D, Kramer J, Cook JL, Childers MK.To test the hypothesis that botulinum toxin type A (BoNT-A) can attenuate lameness associated with acute synovitis in an equine model. Methods: Four horses 2-6 yrs of age with clinically normal carpi were studied for 15 days. Kinematic gait analysis and clinical measures of lameness were conducted before and after experimental interventions. Horses were randomly assigned to either placebo (saline) or treatment (BoNT-A) groups. On day 0 of the intervention, 50 units of BoNT-A or an equivalent volume of saline (0.09%) was given into the middle carpal joints. On day 14, acute synovitis was induce...
Stack JD, Cousty M, Steele E, Handel I, Lechartier A, Vinardell T, David F.Synovial fluid analysis is utilized to diagnose septic synovitis. However, not all cases are clearly and rapidly discernible with the diagnostic tools available in the laboratory. Serum amyloid A (SAA), an acute phase protein, has been shown to be elevated in synovial fluid from inflamed synovial structures. The goal of this study is to describe the correlation between two diagnostic tests measuring equine SAA levels in septic and non-septic synovial structures and to understand the correlation between an elevated SAA result and synovial sepsis. Prospective estimation of sensitivity (Se) and s...
Machado TS, Correia da Silva LC, Baccarin RY, Michelacci YM.Alternative methods to evaluate the joint condition in asymptomatic osteochondrosis dissecans (OCD) and other joint diseases may be useful. Objective: To investigate possible changes in synovial fluid composition that may lead to joint conditions in asymptomatic OCD, in mature horses. Methods: Animals aged >2 years, of different breeds, with OCD in the intermediate ridge of distal tibia, symptomatic or not, were studied. Synovial fluid samples (10 healthy; 11 asymptomatic OCD; 25 symptomatic OCD) were collected by arthroscopy from 29 horses. Glycosaminoglycans (GAGs) were analysed by a comb...
Fietz S, Bondzio A, Moschos A, Hertsch B, Einspanier R.The aim of this study was to develop a specific myeloperoxidase (MPO) activity assay in the synovial fluid of horses and investigate whether MPO activity is increased in different forms of joint diseases. Synovial fluid samples were taken from affected joints from horses with osteoarthritis, chronic non-septic arthritis and septic arthritis, and from healthy control horses. MPO activity was measured using a specific modified o-dianisidine-assay containing 4-aminobenzoic acid hydrazide as a potent and specific inhibitor of the MPO. This assay is characterized by high reproducibility. The result...
Kawcak CE, Frisbie DD, Trotter GW, McIlwraith CW, Gillette SM, Powers BE, Walton RM.To evaluate the effects of arthroscopic surgery, osteochondral fragmentation, and treatment with IV administered hyaluronate on histologic, histochemical, and biochemical measurements within the carpal joints of horses. Methods: 12 clinically normal horses, 2 to 7 years of age. Methods: Horses had an osteochondral fragment created at the distal aspect of the radiocarpal bone of 1 randomly chosen middle carpal joint to simulate osteochondral fragmentation. Horses were treated with 40 mg of hyaluronate or saline solution (placebo) intravenously once a week for 3 consecutive weeks (days 13, 20, a...
Trumble TN, Brown MP, Merritt KA, Billinghurst RC.Validate use of a commercially available immunoassay for measurement of bone alkaline phosphatase (BAP) in equine serum and synovial fluid (SF), and investigate the effects of osteochondral (OC) injury in horses on BAP concentrations in serum and SF. Methods: SF was collected from 37 joints of 34 Thoroughbred (TB) racehorses undergoing arthroscopic surgery for the removal of OC fragments from either the carpal joints (n=18) or the metacarpo-/metatarsophalangeal (MP) joints (n=19). SF was also obtained from 52 joints of 16 normal TB horses, collected bilaterally from carpal joints of 10 horses ...
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...
Taylor SE, Weaver MP, Pitsillides AA, Wheeler BT, Wheeler-Jones CP, Shaw DJ, Smith RK.Quantification of cartilage oligomeric matrix protein (COMP) levels within synovial fluid from the tarsometatarsal joint has not previously been reported and an effective synovial fluid marker would allow monitoring of disease progression and treatment. Objective: To quantify levels of COMP and hyaluronan (HA) in synovial fluid from the tarsometatarsal joint, identify differences in levels from horses with osteoarthritis (OA) of the tarsometatarsal joint compared to a control population and to correlate levels with radiographic changes in horses with OA. Methods: Synovial fluid was collected f...
Byron CR, Stewart MC, Stewart AA, Pondenis HC.To evaluate the effects of glucosamine on equine articular chondrocytes and synoviocytes at concentrations clinically relevant to serum and synovial fluid concentrations. Methods: Articular cartilage and synovium with normal gross appearance from metacarpophalangeal and metatarsophalangeal joints of 8 horses (1 to 10 years of age). Methods: In vitro chondrocyte and synoviocyte cell cultures from 8 horses were treated with glucosamine (0.1 to 20 microg/mL) with or without interleukin-1 (IL-1; 10 ng/mL) for 48 hours. Negative control cultures received no glucosamine or IL-1, and positive control...
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR.Allogeneic and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) have been administered in equine joints for their anti-inflammatory effects. However, allogeneic BMDMSC offer multiple clinical and practical advantages. Therefore, it is important to determine the relative effectiveness of allogeneic vs autologous BMDMSCs. Objective: The objective of the study was to compare the inflamed joint response to autologous vs allogeneic BMDMSCs injections, and to determine if either treatment generated an anti-inflammatory effect. Methods: Randomised controlled study. Methods: Bone marrow...
Skiöldebrand E, Heinegård D, Eloranta ML, Nilsson G, Dudhia J, Sandgren B, Ekman S.The aim of the present study was to correlate the levels of COMP and aggrecan as indicators of tissue damage, in synovial fluid (sf) from carpal joints of acutely lame racehorses, with macroscopical lesions of articular cartilage (OA), osteochondral fractures and ligament tears found at arthroscopy. Sixty-three lame horses [49 Standardbred trotters (STB) and 14 Thoroughbreds (TB)] in conventional training and racing that underwent arthroscopy of their middle carpal or radiocarpal joints were included in the study. Intact as well as fragmented COMP and aggrecan released into the synovial fluid ...
Fuchs B, Bondzio A, Wagner U, Schiller J.Alterations of the phospholipid (PL) compositions of body fluids are assumed to be indicative of inflammatory diseases, e.g. rheumatoid arthritis (RA). Recently, we have shown that particularly the phosphatidylcholine/lysophosphatidylcholine (PC/LPC) ratio determined in human synovial fluids (SF) and sera represents a reliable measure of the inflammatory state in RA patients. However, it is not yet clear to what extent the PC/LPC ratio is also affected by nutrition habits. In the present study, the PL and the corresponding acyl chain compositions of human body fluids (SF and serum of RA patien...
Tulamo RM, Heiskanen T, Salonen M.High molecular weight (MW) hyaluronate (HA) is an integral part of synovial fluid (SF), regulating many important physiologic and pathophysiologic mechanisms. Many of its effects depend on, or are reflected in, the concentration and MW of HA. High-performance liquid chromatography was used to assess simultaneously the concentration and MW of HA in SF obtained from horses with various arthritides: acute traumatic arthritis; chronic traumatic arthritis, including degenerative joint disease (DJD); and infectious arthritis. The size-exclusion column was calibrated, using appropriate HA concentrati...
Misumi K, Vilim V, Hatazoe T, Murata T, Fujiki M, Oka T, Sakamoto H, Carter SD.This study was designed to assay and compare cartilage oligomeric matrix protein (COMP) in horse sera, in samples from normal and joint diseased horses, and to investigate the relationships between COMP in sera and synovial fluids (SF) with keratan sulphate (KS) data. Sera from 38 horses free of any joint pathology (controls) and from horses with aseptic joint disease (AJD horses, n = 40) were assayed for COMP and KS concentrations. Of the 78 horses in the study, 53 were also assayed for COMP and KS concentrations in SF. COMP and KS were measured by inhibition ELISA, using monoclonal antibodie...
Ross-Jones TN, McIlwraith CW, Kisiday JD, Hess TM, Hansen DK, Black J.Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial flu...
van Loon JP, Menke ES, L'ami JJ, Jonckheer-Sheehy VS, Back W, René van Weeren P.Epidural morphine is widely used in veterinary medicine, but there is no information about the anti-hyperalgesic and anti-inflammatory effects in acute inflammatory joint disease in horses. The analgesic, anti-hyperalgesic and anti-inflammatory effects of epidural morphine (100mg/animal or 0.17 ± 0.02 mg/kg) were therefore investigated in horses with acute synovitis. In a cross-over study, synovitis was induced in the talocrural joint by intra-articular lipopolysaccharide (LPS). The effect of epidural morphine was evaluated using physiological, kinematic and behavioural variables. Ranges of m...
Laus F, Gialletti R, Bazzano M, Laghi L, Dini F, Marchegiani A.Osteoarthritis (OA) is a common cause of lameness in sport horses with a significant economic impact. The prevention of OA is crucial since no effective treatment is available. This study aimed to apply untargeted metabolomic analysis to investigate the differences in synovial fluid (SF) composition between healthy and OA-affected joints in horses. SF collected from healthy (n.8) and OA (n.11) horses was analyzed using H-NMR analysis. Metabolomic analysis allowed 55 different metabolites to be identified and quantified in SF samples. Nineteen metabolites were found to be differently concentrat...
Pearson W, Orth MW, Lindinger MI.To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1beta treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. Methods: 22 healthy horses. Methods: 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -...
Haughan J, Jiang Z, Stefanovski D, Moss KL, Ortved KF, Robinson MA.Gene therapy promotes the expression of missing or defective genes and can be curative following administration of a single dose. Gene therapy is prohibited in equine athletes by regulatory bodies due to the high potential for abuse and novel analytical methods are needed for detection. The goal of this study was to detect the administration of an experimental gene therapy: a recombinant adeno-associated viral vector (rAAV) carrying a transgene for the anti-inflammatory cytokine IL-10 (rAAV-IL10). Twelve horses were randomly assigned to receive an intra-articular injection of rAAV-IL10 or phos...
Steel CM, Hunt AR, Adams PL, Robertson ID, Chicken C, Yovich JV, Stick JA.To identify factors affecting the prognosis for survival and athletic use in foals with septic arthritis. Methods: Retrospective study. Methods: 93 foals with septic arthritis. Methods: Medical records were reviewed to obtain clinical findings, laboratory test results, radiographic findings, treatment method, and outcome. Race records for Thoroughbreds and Standardbreds were evaluated to determine whether foals subsequently raced and whether they raced successfully. Results: 43 foals had 1 affected joint, 44 foals had multiple affected joints, and number of affected joints was not recorded for...
Sandker MJ, Duque LF, Redout EM, Chan A, Que I, Löwik CWGM, Klijnstra EC, Kops N, Steendam R, van Weeren R, Hennink WE, Weinans H.In this study, we investigated the use of microspheres with a narrow particle size distribution ('monospheres') composed of biodegradable poly(DL-lactide)-PEG-poly(DL-lactide)-b-poly(L-lactide) multiblock copolymers that are potentially suitable for local sustained drug release in articular joints. Monospheres with sizes of 5, 15 and 30μm and a narrow particle size distribution were prepared by a micro-sieve membrane emulsification process. During in vitro degradation, less crystallinity, higher swelling and accelerated mass loss during was observed with increasing the PEG content of the poly...
Palmer JL, Bertone AL, McClain H.A modification of a colorimetric assay was used to determine synovial fluid total and individual sulphated-glycosaminoglycan concentration in various clinical presentations of joint disease in horses. Concentrations of synovial fluid and serum sulphated-glycosaminoglycan (GAG) were measured by the 1,9-dimethylmethylene blue (DMMB) dye assay in normal horses (n = 49), horses with acute (n = 26) or chronic (n = 27) joint disease (defined by clinical, radiographic, and clinicopathological parameters), and horses with cartilaginous lesions at diagnostic arthroscopy, but with normal radiographs and...
Grady ST, Britton L, Hinrichs K, Nixon AJ, Watts AE.Mesenchymal stem cells (MSCs) improve the osteoarthritis condition, but the fate of MSCs after intra-articular injection is unclear. We used fluorescent nanoparticles (quantum dots [QDs]) to track equine MSCs (QD-labelled MSCs [QD-MSCs]) in vivo after intra-articular injection into normal and osteoarthritic joints. One week after injection of QD-MSCs, unlabelled MSCs, or vehicle, we determined the presence of QD-MSCs in synovium and articular cartilage histologically. In vitro, we evaluated the persistence of QDs in MSCs and whether QDs affected proliferation, immunophenotype, or differentiati...
Reesink HL, Nixon AJ, Su J, Liu S, Sutton RM, Mann S, Watts AE, Peterson RP.Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining we...
Parra-Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S, Belknap JK.To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. Methods: 14 adult horses. Methods: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joi...
Frisbie DD, McIlwraith CW, Kawcak CE, Werpy NM.A randomized blinded placebo controlled trial was conducted to assess the clinical, biochemical and histological effects of a hyaluronan, sodium chondroitin sulfate and N-acetyl-D-glucosamine combination (PG) administered through an intra-articular (IA) route for the treatment of osteoarthritis (OA) at the time of injury. OA was induced in one carpal joint of each of 16 horses. Horses were designated placebo or IA PG treated. All horses were treated with 125 mg amikacin sulfate IA and 5 mL physiological saline in the middle carpal joint bilaterally on study Days 0 (after induction of OA), 7, 1...
