Hyaluronic acid is a naturally occurring glycosaminoglycan found in various tissues and fluids of horses, including synovial fluid, cartilage, and skin. It is involved in maintaining the viscoelastic properties of synovial fluid, contributing to joint lubrication and shock absorption. Hyaluronic acid is often studied for its role in joint health and its potential therapeutic applications in managing equine osteoarthritis and other joint-related conditions. Research explores its physiological functions, the effects of supplementation or intra-articular injections, and its impact on equine locomotion and performance. This page compiles peer-reviewed research studies and scholarly articles that investigate the biological properties, therapeutic potential, and clinical applications of hyaluronic acid in equine medicine.
Goudet G, Bézard J, Duchamp G, Palmer E.In the mare, success rates for the in vitro maturation of oocytes are low. Accordingly, we attempted to determine if immature oocytes could be matured in vivo by injecting them into a preovulatory follicle. Groups of 3-9 oocytes collected from donor mares were transferred under ultrasound control into the preovulatory follicle of a recipient mare that was treated with crude equine pituitary gonadotrophin (CEG) to induce ovulation. Just before ovulation (34 h post treatment) the preovulatory follicle of the recipient mare was punctured to collect both the transferred and the indigenous oocytes ...
Hardy J, Bertone AL, Malemud CJ.To determine the functional response of synovium to infection, and the influence of infected synovium on articular cartilage metabolism. Methods: Synovium and articular cartilage explants from the midcarpal and tarsocrural joints of adult horses. Methods: For experiment 1, synovium explants were incubated as follows: control--incubation in standard medium, infected (I)--incubation with Staphylococcus aureus, and infected-filtered (IF)--incubation with medium collected from the infected group and filtered (0.22-micron filter). Daily collected medium was assayed for interleukin 1 beta (IL-1 beta...
van den Hoogen BM, van Weeren PR, Lopes-Cardozo M, van Golde LM, Barneveld A, van de Lest CH.The amount of uronic acid residues in samples containing glycosaminoglycans or pectin is an important parameter in the quantitative and structural analysis of these complex carbohydrates. This paper describes a method to determine the content of uronic acids in biological samples, using conventional polystyrene microtiter plates and microtiter plate-reading equipment with standard interference filters (i.e., 540 or 492 nm). This assay is a modification of a commonly used procedure, viz. hydrolysis of uronic acid containing carbohydrate polymers in 80% sulfuric acid containing tetraborate ions ...
Tulamo RM, Maisi P.To establish concentration of hyaluronate (HA) in tracheal lavage fluid from healthy horses and horses with chronic obstructive pulmonary disease (COPD). ANIMALS AND SAMPLES: Tracheal lavage fluid samples (n = 42) from 18 horses, 11 with COPD, and 7 control horses. Methods: Clinical examination of the respiratory tract, tracheal lavage, and blood sample collection were performed on horses without clinical signs of respiratory tract disease and horses with clinical signs of COPD. In some horses, 1 to 5 repeated examinations were performed at 1-week intervals. Tracheal lavage fluid samples were ...
Platt D, Wells T, Bayliss MT.Equine chondrocytes were cultured in vitro for 30 days in ionically gelled alginate beads. The alginate polymerises into a stable gel in the presence of divalent cations (calcium), and rapid depolymerisation in the presence of a calcium chelator releases the viable chondrocytes. The chondrocytes maintained a spherical appearance for 30 days in culture, in marked contrast to monolayer cultures, which develop a dedifferentiated fibroblastic morphology. The major proteoglycan molecule produced by the encapsulated chondrocytes was aggrecan, of similar hydrodynamic size to aggrecan molecules presen...
Tulamo RM, Houttu J, Tupamäki A, Salonen M.To investigate the presence of large molecular weight (MW) proteoglycans (PG) and hyaluronate (HA) in synovial fluid (SF) from horses with various arthritides and from control joints. Methods: Horses with acute (< 2 weeks) or chronic (> 4 weeks) lameness were examined by clinical examination, intrasynovial anesthesia, radiography, arthroscopy, and SF analysis. Joints were grouped on the basis of diagnosis: acute traumatic arthritis, chronic traumatic arthritis (with a subgroup of degenerative joint disease), intra-articular fracture, and infectious arthritis. Methods: 31 horses with arthritis ...
Palmer JL, Bertone AL, Malemud CJ, Carter BG, Papay RS, Mansour J.The relevance of site and the influence of exercise on third carpal articular cartilage proteoglycan (PG) were assessed in 16 horses. Six horses were exercised (exercised group) for 30 minutes, 3 times/wk, for 6 weeks. The other 10 horses (nonexercised group) were housed in box stalls for the same 6-week period. At week 6, articular cartilage from the proximal surface of the right third carpal bone was harvested and cultured with radioactive sulfate to label newly synthesized PG. Endogenous PG was measured by use of a uronic acid assay. Newly synthesized and endogenous PG were characterized by...
Muttini A, Petrizzi L, Tinti A, Bertoluzza A.An investigation was carried out on most common synovial fluid parameters of normal and osteochondritic hocks of horses less than 12 months old in order to confirm the presence of an inflammatory process. Furthermore, a spectroscopic study was performed on synovial fluid from both normal and diseased hocks. A depolymerization of hyaluronic acid was demonstrated in synovial fluid from diseases joints, similar to that reported in human rheumatoid arthritis. A one month rest seem to normalize all parameters considered and in one joint, a return to normal infrared spectrum was demonstrated.
Aviad AD, Houpt JB.Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect o...
Timoney JF, Mukhtar MM.The group C streptococci are the most commonly isolated bacteria from disease states in the horse. Important virulence factors of S. equi and S. zooepidemicus are the hyaluronic acid capsule and the antiphagocytic fibrillar M protein located on the surface of the cell wall and extending into and through the capsule. The hyaluronic acid capsule is non-antigenic and so is not involved in protective immunity. The M protein, a superantigen, elicits very strong B and T cell responses that may result in protective immunity mediated by opsonic antibodies in plasma and by locally synthesized IgG and I...
Peloso JG, Stick JA, Caron JP, Peloso PM, Soutas-Little RW.In this double-blind study, the effectiveness of and dose response to intra-articular administration of modified hyaluronan (hylan) was determined in an equine carpal lameness model over a 23-day period, using a computerized three-dimensional motion analysis system, synovial fluid variables, and synovial histologic examination. In 24 clinically sound horses, baseline motion data was acquired from horses trotting at 4 m/s on a high-speed treadmill. Then, to induce lameness, 25 mg of amphotericin B in 5 ml of sterile water was injected into the left middle carpal joint of each horse every other ...
Peyron JG.Viscosupplementation (restoring the rheological properties of a tissue matrix) by injection of hyaluronan into the joints has been in use for 2 decades, mostly for osteoarthritis (OA) of the knee, using doses of 20-25 mg of hyaluronan of 500,000 to 2,500,000 M(r), in sequences of 2 to 10 weekly injections. Pain relief appears in a few days, progresses over a few weeks, and often lasts several months. Some data suggest the benefit can last 6 months to one year. Tolerance is universally reported as very good. Those responding to hyaluronan are 65-80%, compared to 30-35% responding to control. Co...
Lapointe JM, Laverty S, Lavoie JP.Case histories, results of synovial fluid analyses, treatment regimens and outcome are described for 15 adult Standardbred horses with confirmed post-injection septic arthritis. Joint sepsis followed injection of corticosteroids, hyaluronic acid, polysulphated glycosaminoglycan, or local anaesthetic. The median interval from injection to appearance of clinical signs was 2.5 days, and median interval from injection to referral was 9 days. The median initial synovial leucocyte count on admission was 57 x 10(9)/litre, but there was a wide range of values (18-258 x 10(9)/litre). The median synovia...
Rapp HJ, Becker M, Heisse K, Stechele M.This paper reviews the literature and describes our experiences in the diagnosis and treatment of tendinitis in horses. Ultrasonography provides a sensitive tool to diagnose tendinitis and quantitate the degree of damage to the tendon; as well as provide differential diagnoses such as peritendinitis. The principles in therapy of acute tendinitis are: Immediate reduced exercise or rest, physical therapy to reduce inflammation and administration of local and systemic antiinflammatory drugs. The goal is restoration of the tensile strength of the tendon without peritendinous granulation tissue and...
Saari H, Tulamo RM, Konttinen YT, Sorsa T.A high performance liquid chromatography (HPLC) procedure suitable for the simultaneous determination of the molecular size and concentration of macromolecular hyaluronate and proteoglycans in synovial fluid has been developed. Irrigation of the equine tarsocrural joint with 20 ml physiological saline (PSS) caused a mild inflammation with an increase of proteoglycans in the synovial fluid over the baseline arthrocentesis control sample. Proteoglycan and hyaluronate in the synovial fluid did not interact to form hyaluronate-proteoglycan aggregates, but separated as distinct chromatographic peak...
Tulamo RM.Two recently developed direct methods, radioassay-125I-labeled hyaluronic acid binding protein (125I-HABP)- and high-performance liquid chromatography (HPLC), were used to assess and compare the concentration of hyaluronate (HA) in synovial fluid of horses. Also determined were changes in the HA concentration in an experimental treatment model involving physiologic saline solution (PSS)-irrigated or methylprednisolone acetate-injected tarsocrural joints of clinically normal horses. Serum HA concentration was determined simultaneously, using the 125I-HABP assay. Synovial fluid HA concentration ...
Malark JA, Nixon AJ, Skinner KL, Mohammed H.Physical, biochemical, and cytologic properties of synovial fluid from digital flexor tendon sheaths of clinically normal horses were investigated. Tendon sheath fluid was pale yellow, clear, and did not clot. Volume of fluid within a tendon sheath varied minimally, with a mean of 2.11 ml. Total erythrocyte counts were higher than values observed in normal equine joint fluid, whereas values for total leukocyte count (770 +/- 73 cells/mm3), viscosity (6.05 +/- 0.58 cs), and protein concentration (7.87 +/- 0.03 mg/ml) were similar to those in joint fluid. Large mononuclear cells were the predomi...
Welch RD, Watkins JP, DeBowes RM, Leipold HW.The effects of intra-articular administration of dimethylsulfoxide (DMSO) on chemically induced synovitis in the middle carpal joint of 6 weanling horses were evaluated. Following aseptic collection of synovial fluid, the middle carpal joint of each forelimb was injected with 50 mg of Na-monoiodoacetate to induce synovitis. Eight days after injection, synovial fluid was obtained and the right middle carpal joints were injected with 2 ml of 40% DMSO in lactated Ringer solution. The corresponding joints of the left limb (control) were injected with 2 ml of lactated Ringer solution. Sampling and ...
Little CB, Hilbert BJ, Wickstrom S, Hedlund BE.An alcian blue precipitation method for quantifying the hyaluronic acid (HA) and sulphated glycosaminoglycan concentration (SGAG) in solutions containing both compounds was assessed. The assay was found to be rapid and reliable in solutions containing 0 to 200 mg of HA/dl and 50 to 1,000 micrograms of SGAG/dl, and was not affected by the presence of protein, hemoglobin, or methemoglobin in concentrations normally found in synovial fluid. The HA and SGAG concentrations in intercarpal synovial fluid from 13 clinically normal and 11 arthritic horses were evaluated. A relationship was not found be...
Tulamo RM, Saari H, Konttinen YT.Concentration of hyaluronate (HA) in equine serum was determined by a recently developed specific radioassay. The mean +/- SD HA concentration in equine serum was 288 +/- 145 micrograms/L, was age dependent, and varied widely between horses (range, 190 to 760 micrograms/L). Light or moderate exercise increased serum HA concentration from baseline values by 1.5- to 3-fold. In all horses, serum HA concentration returned to or below the original resting values 1 and 2 hours after exercise.
Saari H, Konttinen YT, Tulamo RM, Antti-Poika I, Honkanen V.In addition to its well-known physicochemical properties, hyaluronate (HA) has recently been shown to have important biological and pathophysiologic regulatory effects on granulocytes, monocytes, fibroblasts, and endothelial cells, as well as on the healing of wounds and various joint disorders. Many of these effects depend on or are reflected in the concentration and degree of polymerization of HA. Therefore, high-performance liquid chromatography with size-exclusion column was used to characterize the concentration and degree of polymerization of HA in equine synovial fluid (SF). The mean (+...
Balazs EA, Denlinger JL.The availability of elastoviscous solutions of highly purified hyaluronan has created two new therapeutic methods in human and veterinary medicine: viscosurgery and viscosupplementation. Viscosurgical tools and implants are widely used in ophthalmology and have been suggested for use in otology. Visco-supplementation of joint fluid using elastoviscous hyaluronan solutions is widely used in the treatment of equine traumatic arthritis. It was also suggested for use in idiopathic osteoarthritis in humans, but this application has not received wide acceptance. Cross-linked forms of hyaluronan have...
White KK, Hodgson DR, Hancock D, Parry BW, Cordell C.The effects of repeated arthrocentesis and injection of local anesthetic agents, lidocaine HCl or mepivacaine HCl on the equine middle carpal joint were investigated. Synovial fluid samples were evaluated before, and 12, 24 and 48 hours following, treatment. The greatest changes from pretreatment values occurred in synovial fluid cellularity. Repeated arthrocentesis caused a moderate increase in cell counts, while injection of local anesthetics caused a greater increase. Alterations in mucin clot quality, hyaluronic acid content, fluid viscosity, total protein and immunoglobulin G were general...
Hardy J, Marcoux M, Eisenberg H.A suspected lesion of osteochondrosis dissecans involving the anconeal process of the humeroradial joint (elbow) was found in 2 horses. In horse 1, the lesion was found during routine lameness examination, during which alleviation of the lameness was achieved after intra-articular anesthesia of the elbow. In horse 2, the lesion was found at necropsy. Horse 1 responded satisfactorily to intra-articular treatment with hyaluronic acid. Both horses also had other joints affected with osteochondrosis dissecans.
Hilbert BJ, Rowley G, Antonas KN, McGill CA, Reynoldson JA, Hawkins CD.Sodium hyaluronate was injected into normal horse joints and joints that had undergone an arthrotomy and experimental cartilage damage. The elimination half-life for hyaluronic acid in normal joints was found to be approximately 96 h. The injection caused a non-significant increase (42%) in synovial fluid protein concentration and a fall in the intrinsic viscosity of the fluid. In the arthrotomy group the synovial fluid hyaluronic acid concentration fell after surgery but it was unaffected by the injection of sodium hyaluronate. An initial rise in the intrinsic viscosity of the synovial fluid ...
Owen RA, Marsh JA, Hallett FR, Lumsden JH, Johnson J.Methylprednisolone acetate was injected repeatedly into both intercarpal joints of a horse that had a 3rd carpal bone fracture in 1 limb. Synovial fluid from intercarpal and radiocarpal joints of both limbs were obtained serially for study. Arthropathy developed in the fractured joint following prolonged corticosteroid therapy and exercise. In the corticosteroid-injected normal joint, the hyaluronic acid concentration initially decreased, then increased. A depletion in cartilage matrix was seen at necropsy, 175 days after onset of treatment. Determination of total protein content in synovial f...
Hilbert BJ, Rowley G, Antonas KN.A method previously described was used to determine the hyaluronic acid concentration in synovia from normal and arthritic horse joints. The concentration of hyaluronic acid in the synovia from arthritic joints was found to be significantly lower than the concentration in fluid from normal joints.
Rowley G, Antonas KN, Hilbert BJ.An assay for the determination of hyaluronic acid concentration in equine synovia (synovial fluid) was investigated. The method involved the degradation of hyaluronic acid, using a highly specific microbial enzyme. The unsaturated tetra- and hexasaccharide products were oxidized with periodate and caused to react with thiobarbituric acid for form a chromophore which absorbed in the visible range of the spectrum. The method was precise within acceptable limits for synovia and compared favorably with the widely used carbazole method of Bitter and Muir (Anal Biochem 4:330-334, 1962). The between-...
Nizolek DJ, White KK.Degenerative arthrosis is perhaps the most common debilitating disease of performance horses. Treatment should be based upon a knowledge of the anatomy and physiology of normal joints and upon an understanding of the processes of degeneration and repair. These topics are briefly reviewed. Although rest is probably, the most beneficial therapy, physical and pharmaceutical treatments are often employed in an effort to speed recovery. The effects and relative benefits of intrasynovial injections of corticosteroids, hyaluronica cid, and Arteparon are considered in detail. Although local corticoste...
Gingerich DA, Auer JA, Fackelman GE.A single intra-articular injection of 20 or 40 mg of purified hyaluronic acid of rooster comb origin resulted in restoration of normal joint function in horses with experimentally induced osteoarthritis. The functional improvement, measured by pressure sensitive force plate techniques, was detectable within one week after treatment and persisted throughout a four week experimental period despite continued use of the joints. The response was dose dependent in that injection of 0 (saline), 5 or 10 mg hyaluronic acid per joint space resulted in no significant change in joint function while dosage...
Richardson DW, Loinaz R.There is an enormous volume of published material about most of the agents used to treat or prevent arthritis in horses. Unfortunately, most of the claims made by nearly all purveyors of arthritis medications in such media are largely unsubstantiated. In addition, the quality of the available information is highly inconsistent, making evidence-based recommendations difficult. This article concentrates on injectable polysulfated glycosaminoglycan, injectable hyaluronan, and the common oral "nutraceuticals".
Muttini A, Petrizzi L, Tinti A, Bertoluzza A.An investigation was carried out on most common synovial fluid parameters of normal and osteochondritic hocks of horses less than 12 months old in order to confirm the presence of an inflammatory process. Furthermore, a spectroscopic study was performed on synovial fluid from both normal and diseased hocks. A depolymerization of hyaluronic acid was demonstrated in synovial fluid from diseases joints, similar to that reported in human rheumatoid arthritis. A one month rest seem to normalize all parameters considered and in one joint, a return to normal infrared spectrum was demonstrated.
Rapp HJ, Becker M, Heisse K, Stechele M.This paper reviews the literature and describes our experiences in the diagnosis and treatment of tendinitis in horses. Ultrasonography provides a sensitive tool to diagnose tendinitis and quantitate the degree of damage to the tendon; as well as provide differential diagnoses such as peritendinitis. The principles in therapy of acute tendinitis are: Immediate reduced exercise or rest, physical therapy to reduce inflammation and administration of local and systemic antiinflammatory drugs. The goal is restoration of the tensile strength of the tendon without peritendinous granulation tissue and...
Tyrnenopoulou PC, Rizos ED, Kritsepi-Konstantinou M, Papadopoulou PL, Patsikas MN, Papazoglou LG, Aggeli A, Diakakis NE.To determine whether differences existed in the viscoelastic properties of synovial fluid samples from the metacarpophalangeal, intercarpal, and distal interphalangeal joints of orthopedically normal athletic horses. Methods: 45 warmblood horses and 30 Thoroughbreds (age range, 4 to 16 years). Methods: Synovial fluid samples were aseptically obtained via arthrocentesis from 1 metacarpophalangeal, intercarpal, and distal interphalangeal joint of each horse, and nucleated cell counts were performed. A commercial ELISA was used to measure sample hyaluronic acid concentrations, and full rheologica...
Fortier LA.Systemic therapies for joint disease may be prescribed when a single joint is involved or when multiple sites are affected. The precise therapeutic regimen recommended depends on the duration,cause, and site(s) of injury and is often an adjunct to intra-articular or supportive therapies. If the clinical signs of joint disease are acute and moderate in severity, nonsteroidal anti-inflammatory drugs are often administered to alleviate pain and inflammation. When aiming for more of a generalized maintenance or chondro-protective regimen, an alternative medication, such as hyaluronan,polysulfated ...
Listoni AJ, Arruda I, Maia L, Barberini DJ, Martins I, Vasconcellos FC, Landim-Alvarenga FC.Nanotechnology techniques have a prominent role in the current technical and scientific scene. The layer-by-layer (LbL) deposition allows obtaining nanostructures with sophisticated multilayer, using a simple, but versatile technique. This procedure, which is used to coat and functionalize surfaces with nanometer- thick films, has applications in bioengineering, medicine, chemistry, materials and chemical engineering among other areas. Chitosan is a biomaterial, coming from the chitin, a very abundant polymer in nature, which has been recently tested as scaffolds. In this experiment we test th...
Marsh CA, Schneider RK, Sampson SN, Roberts GD.To determine treatment outcome on the basis of pathological changes identified on MRI and lameness duration in horses with navicular syndrome that underwent injection of corticosteroid and hyaluronan into the navicular bursa. Methods: Retrospective case series. Methods: 101 horses with navicular syndrome. Methods: Medical records of horses with signs of navicular syndrome evaluated between January 2000 and December 2008 were reviewed. Data on signalment, use of the horse, history, affected limbs, duration of lameness, findings on lameness examination, radiographic findings, MRI findings, treat...
Platt D, Wells T, Bayliss MT.Equine chondrocytes were cultured in vitro for 30 days in ionically gelled alginate beads. The alginate polymerises into a stable gel in the presence of divalent cations (calcium), and rapid depolymerisation in the presence of a calcium chelator releases the viable chondrocytes. The chondrocytes maintained a spherical appearance for 30 days in culture, in marked contrast to monolayer cultures, which develop a dedifferentiated fibroblastic morphology. The major proteoglycan molecule produced by the encapsulated chondrocytes was aggrecan, of similar hydrodynamic size to aggrecan molecules presen...
Sladek S, Kearney C, Crean D, Brama PAJ, Tajber L, Fawcett K, Labberte MC, Leggett B, Brayden DJ.Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions ...
Lamkin I, Pugliese B, Nystrom J, Fubini SL, Knickelbein KE.To describe the successful restoration of superior eyelid function in a horse following traumatic avulsion using an advancement flap blepharoplasty and subdermal hyaluronic acid filler. Methods: A 21-year-old American Paint Horse stallion who was attacked by a fellow stallion resulting in numerous traumatic injuries including avulsion of approximately 75% of the left superior eyelid. Methods: With standing sedation and locoregional anesthesia, the superior eyelid wound was debrided and an advancement flap blepharoplasty (H-plasty) and temporary tarsorrhaphy were performed. Routine healing of t...
Pien N, Van de Maele Y, Parmentier L, Meeremans M, Mignon A, De Schauwer C, Peeters I, De Wilde L, Martens A, Mantovani D, Van Vlierberghe S....Hand tendon injuries represent a major clinical problem and might dramatically diminish a patient's life quality. In this study, a targeted solution for flexor tendon repair was developed by combining a mechanical and biological approach. To this end, a novel acrylate-endcapped urethane-based polymer (AUP) was synthesized and its physico-chemical properties were characterized. Next, tubular repair constructs were developed using electrospinning of the AUP material with incorporated naproxen and hyaluronic acid (i.e. anti-inflammatory and anti-adhesion compounds, respectively), and with a tubul...
Niemelä TM, Tulamo RM, Hielm-Björkman AK.Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) an...
de Souza AF, Paretsis NF, De Zoppa ALDV.A systematic review was conducted to investigate evidence to support or refute the use of hyaluronic acid and polyacrylamide hydrogel as intra-articular therapy in equines, which are frequent treatment options in the routine of veterinarians of equines in cases of osteoarthritis. In total, 19 studies were included, among clinical and in vitro studies, as well as a retrospective series of cases. The outcomes of the included studies provided fragile evidence supporting the recommendation for intra-articular use of hyaluronic acid. No study was included showing any clinical outcome in diseased s...
Mustonen AM, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkänen A, Paakkonen T, Rilla K, Niemelä T, Nieminen P.Osteoarthritis (OA) is a degenerative joint disease with inadequately understood pathogenesis leading to pain and functional limitations. Extracellular vesicles (EVs) released by synovial joint cells can induce both pro- and anti-OA effects. Hyaluronic acid (HA) lubricates the surfaces of articular cartilage and is one of the bioactive molecules transported by EVs. In humans, altered EV counts and composition can be observed in OA synovial fluid (SF), while EV research is in early stages in the horse-a well-recognized OA model. The aim was to characterize SF EVs and their HA cargo in 19 horses...
Yang G, Prestwich GD, Mann BK.The progression of wound healing is a complicated but well-known process involving many factors, yet there are few products on the market that enhance and accelerate wound healing. This is particularly problematic in veterinary medicine where multiple species must be treated and large animals heal slower, oftentimes with complicating factors such as the development of exuberant granulation tissue. In this study a crosslinked-hyaluronic-acid (HA-) based biomaterial was used to treat wounds on multiple species: rats, dogs, and horses. The base molecule, thiolated carboxymethyl HA, was first foun...
Frean SP, Lees P.To investigate effects of the anti-arthritic agents hyaluronan and polysulfated glycosaminoglycan (PSGAG) on inflammatory metabolism in cultured equine synoviocytes. Methods: Synoviocytes cultured from samples obtained from the metacarpophalangeal joints of 4 horses. Methods: Equine synoviocytes were grown in monolayer culture. Synoviocytes were stimulated with lipopolysaccharide (LPS) and simultaneously treated with various concentrations of hyaluronan or PSGAG for 48 hours. Three hyaluronan preparations were compared. Prostaglandin E2 (PGE2) concentrations in culture medium were measured, us...
Rodriguez Hurtado I, Stewart AJ, Wolfe DF, Caldwell FJ, Harrie M, Whitley EM.Hyaluronan (HA), a glycosaminoglycan, is a major component of the pericellular matrix which envelopes mammalian cells. Binding of hyaluronan to one of its specific receptors, CD44, modulates transduction of intracellular signals which direct a variety of processes, including embryogenesis, wound healing, inflammation, and neoplasia. Since regulation of these processes is critical to equine reproductive success, localization of constitutive CD44 expression was evaluated by immunohistochemical methods in ovarian, oviductal, and uterine tissues from healthy mares. Ovarian stroma contained thecal ...
Malark JA, Nixon AJ, Skinner KL, Mohammed H.Physical, biochemical, and cytologic properties of synovial fluid from digital flexor tendon sheaths of clinically normal horses were investigated. Tendon sheath fluid was pale yellow, clear, and did not clot. Volume of fluid within a tendon sheath varied minimally, with a mean of 2.11 ml. Total erythrocyte counts were higher than values observed in normal equine joint fluid, whereas values for total leukocyte count (770 +/- 73 cells/mm3), viscosity (6.05 +/- 0.58 cs), and protein concentration (7.87 +/- 0.03 mg/ml) were similar to those in joint fluid. Large mononuclear cells were the predomi...
Saari H, Konttinen YT, Tulamo RM, Antti-Poika I, Honkanen V.In addition to its well-known physicochemical properties, hyaluronate (HA) has recently been shown to have important biological and pathophysiologic regulatory effects on granulocytes, monocytes, fibroblasts, and endothelial cells, as well as on the healing of wounds and various joint disorders. Many of these effects depend on or are reflected in the concentration and degree of polymerization of HA. Therefore, high-performance liquid chromatography with size-exclusion column was used to characterize the concentration and degree of polymerization of HA in equine synovial fluid (SF). The mean (+...
Grissom MJ, Temple-Wong MM, Adams MS, Tom M, Schumacher BL, McIlwraith CW, Goodrich LR, Chu CR, Sah RL.Following various types of naturally-occurring traumatic injury to an articular joint, the lubricating ability of synovial fluid is impaired, with a correlated alteration in the concentration and/or structure of lubricant molecules, hyaluronan and proteoglycan-4. However, the effect of arthroscopic cartilage repair surgery on synovial fluid lubricant function and composition is unknown. Objective: Arthroscopic treatment of full-thickness chondral defects in horses with (1) platelet-enriched fibrin or (2) platelet-enriched fibrin+mesenchymal stem cells leads to equine synovial fluid with impair...
Hilbert BJ, Rowley G, Antonas KN, McGill CA, Reynoldson JA, Hawkins CD.Sodium hyaluronate was injected into normal horse joints and joints that had undergone an arthrotomy and experimental cartilage damage. The elimination half-life for hyaluronic acid in normal joints was found to be approximately 96 h. The injection caused a non-significant increase (42%) in synovial fluid protein concentration and a fall in the intrinsic viscosity of the fluid. In the arthrotomy group the synovial fluid hyaluronic acid concentration fell after surgery but it was unaffected by the injection of sodium hyaluronate. An initial rise in the intrinsic viscosity of the synovial fluid ...
Gingerich DA, Auer JA, Fackelman GE.A single intra-articular injection of 20 or 40 mg of purified hyaluronic acid of rooster comb origin resulted in restoration of normal joint function in horses with experimentally induced osteoarthritis. The functional improvement, measured by pressure sensitive force plate techniques, was detectable within one week after treatment and persisted throughout a four week experimental period despite continued use of the joints. The response was dose dependent in that injection of 0 (saline), 5 or 10 mg hyaluronic acid per joint space resulted in no significant change in joint function while dosage...
Yuda Y, Kasashima Y, Kuwano A, Sato K, Hattori S, Arai K.Upregulation of hyaluronidase 2 (HYAL2), one of somatic hyaluronidase (HAase), was demonstrated in granulation tissue during the healing of equine superficial digital flexor tendon injuries. The activity of HAase was assessed by hyaluronan (HA)-containing gel zymography and in situ zymography using frozen sections obtained from normal and injured tendon tissues. Elevated HAase activity was identified in the extract from the tendinopathic tissues, with lower levels of the activity in normal tendons. In situ zymography using fluorescently-labeled HA demonstrated HAase activity in the granulation...
Munsterman AS, Kottwitz JJ, Reid Hanson R.To determine the efficacy of adhesion barriers in horses using quantitative statistical analysis. Methods: Meta-analytical review. Methods: A search using PubMed/MEDLINE and Google Scholar was performed, followed by secondary searches of veterinary trade journals, bibliographies of relevant articles, manufacturer websites, and technical reference guides. Randomized experimental trials in healthy horses were considered that included both a treatment and control group. The endpoint required was euthanasia or laparoscopy to identify adhesion formation. A meta-analysis was performed using a random...
Velloso Alvarez A, Boone LH, Braim AP, Taintor JS, Caldwell F, Wright JC, Wooldridge AA.There are several non-steroidal intra-articular therapeutics (NSIATs) available for use by equine practitioners for the treatment of performance-limiting joint-related pathology. Information is limited on perceived clinical efficacy, recommended treatment protocols, and associated complications. Our objective with this cross-sectional survey was to investigate the current clinical usage of NSIATs by equine practitioners. An electronic cross-sectional convenience survey inquiring about the use of steroidal and NSIATS (platelet-rich plasma, autologous conditioned serum, autologous protein soluti...
Clegg PD, Jones MD, Carter SD.Loss of articular cartilage, which is the most important pathological lesion occurring in osteoarthritis, has been shown to be enzymatically mediated. The matrix metalloproteinases (MMPs) are a group of enzymes which have been implicated in this degradation of articular cartilage matrix. The use of pharmacological agents to inhibit this catabolic process in the joint is a potential route for therapeutic intervention. The gelatinase MMPs, MMPs-2 and 9, were purified by affinity chromatography from equine cell cultures. The ability of phenylbutazone, flunixin, betamethasone, dexamethasone, methy...
Peyron JG.Viscosupplementation (restoring the rheological properties of a tissue matrix) by injection of hyaluronan into the joints has been in use for 2 decades, mostly for osteoarthritis (OA) of the knee, using doses of 20-25 mg of hyaluronan of 500,000 to 2,500,000 M(r), in sequences of 2 to 10 weekly injections. Pain relief appears in a few days, progresses over a few weeks, and often lasts several months. Some data suggest the benefit can last 6 months to one year. Tolerance is universally reported as very good. Those responding to hyaluronan are 65-80%, compared to 30-35% responding to control. Co...
Porcello A, Gonzalez-Fernandez P, Jordan O, Allémann E.Hyaluronic acid (HA) constitutes a versatile chemical framework for the development of osteoarthritis pain treatment by means of injection in the joints, so-called viscosupplementation. Without appropriate physico-chemical tuning, such preparations are inherently hindered by prompt in vivo degradation, mediated by hyaluronidases and oxidative stress. To prolong hydrogel residence time and confer optimized product functionality, novel thermoresponsive nanoforming HA derivatives were proposed and characterized. Combined use of sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacryl...
Viitanen M, Bird J, Makela O, Schramme M, Smith R, Tulamo RM, May S.The purpose of this study was to investigate biochemical changes in synovial fluid in navicular disease, and to establish if synovial fluid from the distal interphalangeal joint (DIP) could be used diagnostically to assess alterations in the synovial fluid of the navicular bursa. Cartilage oligomeric matrix protein (COMP), total glycosaminoglycans (GAG), hyaluronan (HA), metalloproteinases 2 and -9 (MMP-2 and MMP-9) and total protein (TP) levels were determined in synovial fluids obtained from 18 navicular bursae and 35 DIP -joints from animals suffering from navicular disease, and the same sy...
Tung JT, Venta PJ, Eberhart SW, Yuzbasiyan-Gurkan V, Alexander L, Caron JP.To determine the effects of recombinant equine interleukin -1beta (reIL-1beta) and 4 anti-inflammatory compounds on the expression and activity of cyclooxygenase (COX)-2 in cultured equine chondrocytes. Methods: Articular cartilage from 9 young adult horses. Methods: Reverse transcriptase-polymerase chain reaction methods were used to amplify a portion of equine COX-2 to prepare a cDNA probe. Northern blot analysis was used to quantify the expression of COX-2 in first-passage cultures of equine articular chondrocytes propagated in media containing dexamethasone (DEX), phenylbutazone (PBZ), pol...
