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Topic:Metalloproteinases

Metalloproteinases are a group of enzymes found in horses that are involved in the breakdown of extracellular matrix components. These enzymes, which include matrix metalloproteinases (MMPs), play a role in various physiological and pathological processes, such as tissue remodeling, wound healing, and inflammation. Metalloproteinases are regulated by tissue inhibitors of metalloproteinases (TIMPs), which help maintain a balance between matrix degradation and synthesis. Alterations in metalloproteinase activity can be associated with conditions such as osteoarthritis and laminitis in horses. This page compiles peer-reviewed research studies and scholarly articles that investigate the function, regulation, and clinical implications of metalloproteinases in equine health.
Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study.
Arthritis research & therapy    March 9, 2009   Volume 11, Issue 2 R35 doi: 10.1186/ar2640
de Grauw JC, van de Lest CH, van Weeren PR.Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation. Methods: Localized inflammation was induced in the intercarpal joi...
Matrix metalloproteinases in inflammatory pathologies of the horse.
Veterinary journal (London, England : 1997)    December 3, 2008   Volume 183, Issue 1 27-38 doi: 10.1016/j.tvjl.2008.09.022
Clutterbuck AL, Harris P, Allaway D, Mobasheri A.The extracellular matrix (ECM) of connective tissue is constantly being remodelled to allow for growth and regeneration. Normal tissue maintenance requires the ECM components to be degraded and re-synthesised in relatively equal proportions. This degradation is facilitated by matrix metalloproteinases (MMPs) and their proteolytic action is controlled primarily by the tissue inhibitors of metalloproteinases (TIMPs). Both MMPs and TIMPs exist in a state of dynamic equilibrium, with a slight excess of one or the other depending on the need for either ECM breakdown or synthesis. Long-term disrupti...
Effects of clinically relevant concentrations of glucosamine on equine chondrocytes and synoviocytes in vitro.
American journal of veterinary research    September 4, 2008   Volume 69, Issue 9 1129-1134 doi: 10.2460/ajvr.69.9.1129
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...
Determination of MMP-2 and -9 activities in synovial fluid of horses with osteoarthritic and arthritic joint diseases using gelatin zymography and immunocapture activity assays.
Equine veterinary journal    December 20, 2007   Volume 40, Issue 3 266-271 doi: 10.2746/042516408X251921
Fietz S, Einspanier R, Hoppner S, Hertsch B, Bondzio A.Matrix metalloproteinases (MMPs)-2 and -9 activities have been found elevated in synovial fluid from various joint diseases in man. However, in the horse few data are available. Objective: To explore the clinical significance of MMP-2 and -9 activities in synovial fluid of horses with different forms of joint diseases. Methods: Gelatin zymography and MMP-2 and -9 immunocapture activity assays were applied on synovial fluids from control joints and joints with aseptic joint disease (AJD) and septic arthritis (SA). Additionally, MMP-2 and -9 activities were measured in samples from SA to monitor...
The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis.
Veterinary journal (London, England : 1997)    October 29, 2007   Volume 179, Issue 1 10-24 doi: 10.1016/j.tvjl.2007.08.013
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...
Use of matrix metalloproteinases 2 and 9 and white blood cell counts in monitoring the treatment and predicting the survival of horses with septic arthritis.
The Veterinary record    September 11, 2007   Volume 161, Issue 10 329-334 doi: 10.1136/vr.161.10.329
Kidd JA, Barr AR, Tarlton JF.Thirty-nine samples of synovial fluid were collected from the joints of 32 horses with suspected septic arthritis and 39 samples were collected from horses euthanased for non-orthopaedic conditions. The white blood cell counts (WBCC) were determined and the pro and active forms of matrix metalloproteinases (MMPs) 2 and 9 were measured by gelatin zymography and image analysis in each sample. The initial measurements of the ratio of proMMP9:proMMp2 and WBCC were good prognostic indicators of the survival of the horses. There was no significant relationship between the interval between the injury...
Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity.
Aging cell    June 18, 2007   Volume 6, Issue 4 547-556 doi: 10.1111/j.1474-9726.2007.00307.x
Dudhia J, Scott CM, Draper ER, Heinegård D, Pitsillides AA, Smith RK.Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collide in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine ten...
In vitro inhibition of matrix metalloproteinase activity in tracheal epithelial lining fluid from horses with recurrent airway obstruction.
American journal of veterinary research    July 5, 2006   Volume 67, Issue 7 1252-1257 doi: 10.2460/ajvr.67.7.1252
Raulo SM, Sorsa T, Maisi P.To evaluate inhibitory effects of synthetic matrix metalloproteinase (MMP) inhibitors in vitro on gelatinolytic and collagenolytic activities in tracheal epithelial lining fluid (TELF) of horses with recurrent airway obstruction (RAO). Methods: 10 horses with RAO and 5 healthy control horses. Methods: Substrate-based functional assays, collagen I and gelatin degradation, were used to measure endogenous collagenolytic and gelatinolytic activities in TELF. In vitro inhibition of MMP activity in TELF with 2 chemically modified tetracyclines (CMTs; CMT-3 and CMT-8) and 2 bisphosphonates (BPs; zole...
Effects of glucosamine and chondroitin sulfate on mediators of osteoarthritis in cultured equine chondrocytes stimulated by use of recombinant equine interleukin-1beta.
American journal of veterinary research    December 13, 2005   Volume 66, Issue 11 1861-1869 doi: 10.2460/ajvr.2005.66.1861
Neil KM, Orth MW, Coussens PM, Chan PS, Caron JP.To determine whether glucosamine and chondroitin sulfate (CS) at concentrations approximating those achieved in plasma by oral administration would influence gene expression of selected mediators of osteoarthritis in cytokine-stimulated equine articular chondrocytes. Methods: Samples of grossly normal articular cartilage obtained from the metacarpophalangeal joint of 13 horses. Methods: Equine chondrocytes in pellet culture were stimulated with a subsaturating dose of recombinant equine interleukin (reIL)-1beta. Effects of prior incubation with glucosamine (2.5 to 10.0 microg/mL) and CS (5.0 t...
Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide-induced alterations in articular cartilage metabolism.
Osteoarthritis and cartilage    February 25, 2005   Volume 13, Issue 3 250-257 doi: 10.1016/j.joca.2004.12.004
Petrov R, MacDonald MH, Tesch AM, Benton HP.To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage. Methods: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 microM), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adeno...
Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1.
Equine veterinary journal    January 18, 2005   Volume 37, Issue 1 19-25 doi: 10.2746/0425164054406919
van den Boom R, van der Harst MR, Brommer H, Brama PA, Barneveld A, van Weeren PR, DeGroot J.Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker ...
In vitro effects of oxytetracycline on matrix metalloproteinase-1 mRNA expression and on collagen gel contraction by cultured myofibroblasts obtained from the accessory ligament of foals.
American journal of veterinary research    April 14, 2004   Volume 65, Issue 4 491-496 doi: 10.2460/ajvr.2004.65.491
Arnoczky SP, Lavagnino M, Gardner KL, Tian T, Vaupel ZM, Stick JA.To determine the effects of oxytetracycline on matrix metalloproteinase-1 (MMP-1) mRNA expression and collagen gel contraction by equine myofibroblasts in an effort to explain the mechanistic basis for the pharmacologic treatment of flexural deformities in foals. Methods: Cultured myofibroblasts from the accessory ligament (distal check ligament) of 6 foals. Methods: Collagen gel scaffolds seeded with equine myofibroblasts were cultured in individual culture dishes containing complete media (Dulbecco's modified Eagle medium with 10% fetal bovine serum) and oxytetracycline (0, 12.5, 25, or 75 m...
The influence of repeated arthrocentesis and exercise on matrix metalloproteinase and tumour necrosis factor alpha activities in normal equine joints.
Equine veterinary journal    March 25, 2004   Volume 36, Issue 2 155-159 doi: 10.2746/0425164044868602
van den Boom R, Brama PA, Kiers GH, DeGroot J, Barneveld A, van Weeren RR.Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) may be useful as biomarkers of joint disease or inflammation. However, activity of both MMPs and TNF-alpha in synovial fluid (SF) may be influenced by nonpathological factors such as arthrocentesis or exercise. Objective: To investigate the influence of repeated arthrocentesis and exercise on MMP and TNF-alpha activities in SF from normal equine joints. Methods: SF was collected from the left metacarpophalangeal, radiocarpal and tarsocrural joints of 16 horses. Eight of these horses were subsequently subjected to an ...
Factors regulating collagen synthesis and degradation during second-intention healing of wounds in the thoracic region and the distal aspect of the forelimb of horses.
American journal of veterinary research    November 14, 2002   Volume 63, Issue 11 1564-1570 doi: 10.2460/ajvr.2002.63.1564
Schwartz AJ, Wilson DA, Keegan KG, Ganjam VK, Sun Y, Weber KT, Zhang J.To determine significant molecular and cellular factors responsible for differences in second-intention healing in thoracic and metacarpal wounds of horses. Methods: 6 adult mixed-breed horses. Methods: A full-thickness skin wound on the metacarpus and another such wound on the pectoral region were created, photographed, and measured, and tissue was harvested from these sites weekly for 4 weeks. Gene expression of type-I collagen, transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP)-1, and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by quantitative in situ ...
Evaluation of the influence of prostaglandin E2 on recombinant equine interleukin-1beta-stimulated matrix metalloproteinases 1, 3, and 13 and tissue inhibitor of matrix metalloproteinase 1 expression in equine chondrocyte cultures.
American journal of veterinary research    July 18, 2002   Volume 63, Issue 7 987-993 doi: 10.2460/ajvr.2002.63.987
Tung JT, Arnold CE, Alexander LH, Yuzbasiyan-Gurkan V, Venta PJ, Richardson DW, Caron JP.To determine the effects of prostaglandin E2 (PGE2) on recombinant equine interleukin (IL)-1beta-stimulated expression of matrix metalloproteinases (MMP 1, MMP 3, MMP 13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in vitro. Methods: Cultured equine chondrocytes. Methods: Stationary monolayers of first-passage chondrocytes were exposed to graduated concentrations of PGE2 with or without a subsaturating dose (50 pg/ml) of recombinant equine IL-1beta (reIL-1beta) to induce expression of MMP 1, MMP 3, MMP 13, and TIMP 1, followed by RNA isolation and northern blotting. In subseque...
Synovial fluid studies in navicular disease.
Research in veterinary science    January 19, 2002   Volume 71, Issue 3 201-206 doi: 10.1053/rvsc.2001.0509
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...
Synovial fluid gelatinase concentrations and matrix metalloproteinase and cytokine expression in naturally occurring joint disease in horses.
American journal of veterinary research    September 19, 2001   Volume 62, Issue 9 1467-1477 doi: 10.2460/ajvr.2001.62.1467
Trumble TN, Trotter GW, Oxford JR, McIlwraith CW, Cammarata S, Goodnight JL, Billinghurst RC, Frisbie DD.To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[IL]-1alpha and beta; and tumor necrosis factor (TNF)-alpha in synovial membrane and articular cartilage from horses with naturally occurring joint disease. Methods: Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). Methods: Synovial fluid gelatinase concentra...
Evaluation of collagenase activity, matrix metalloproteinase-8, and matrix metalloproteinase-13 in horses with chronic obstructive pulmonary disease.
American journal of veterinary research    July 17, 2001   Volume 62, Issue 7 1142-1148 doi: 10.2460/ajvr.2001.62.1142
Raulo SM, Sorsa TA, Kiili MT, Maisi PS.To determine collagenase activity and evaluate matrix metalloproteinase (MMP)-8 and MMP-13 in horses with chronic obstructive pulmonary disease (COPD). Methods: 12 horses with COPD and 12 healthy control horses. Methods: Collagenase activity was determined by use of an assay for degradation of type-I collagen. Western immunoblot analysis was used to identify interstitial collagenases MMP-8 and MMP-13 in tracheal epithelial lining fluid (TELF). Immunocytochemistry and in situ hybridization were used to determine cellular expression of these 2 collagenases in cells in bronchoalveolar lavage flui...
In vitro evidence for a bacterial pathogenesis of equine laminitis.
Veterinary microbiology    March 10, 2001   Volume 79, Issue 3 209-223 doi: 10.1016/s0378-1135(00)00359-x
Mungall BA, Kyaw-Tanner M, Pollitt CC.Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic ex...
Concentrations of elastinolytic metalloproteinases in respiratory tract secretions of healthy horses and horses with chronic obstructive pulmonary disease.
American journal of veterinary research    September 8, 2000   Volume 61, Issue 9 1067-1073 doi: 10.2460/ajvr.2000.61.1067
Raulo SM, Sorsa TA, Maisi PS.To determine whether samples of tracheal epithelial lining fluid (TELF) obtained from horses have elastinolytic activity characteristic of metalloproteinases, to compare elastinolytic activity in TELF obtained from healthy horses and horses with chronic obstructive pulmonary disease (COPD), and to determine whether chemically modified tetracycline-3 (CMT-3) inhibits elastinolytic activity in TELF ANIMALS: 10 horses with COPD and 10 healthy control horses. Methods: Zymography and fluorometry were used to measure elastinolytic activity, and EDTA was used to inhibit elastinolytic activity and ver...
Differences in the concentration of various synovial fluid constituents between the distal interphalangeal joint, the metacarpophalangeal joint and the navicular bursa in normal horses.
Research in veterinary science    August 5, 2000   Volume 69, Issue 1 63-67 doi: 10.1053/rvsc.2000.0385
Viitanen M, Bird J, Maisi P, Smith R, Tulamo RM, May S.As a prerequisite for the identification of navicular disease markers, the concentrations of cartilage oligomeric matrix protein (COMP), total glycosaminoglycans (GAG), hyaluronan, metalloproteinases (MMP) 2 and 9 and total protein were measured in synovial fluid samples obtained from the distal interphalangeal joint (DIP), the metacarpophalangeal joint (MCP) and the navicular bursa of 24 horses. Mean GAG, COMP and total protein levels were significantly higher in the DIP joint and in the navicular bursa compared to the MCP joint. Hyaluronan content was lower. MMP -2 activity was present in al...
Inhibition of articular cartilage degradation in culture by a novel nonpeptidic matrix metalloproteinase inhibitor.
Annals of the New York Academy of Sciences    July 23, 1999   Volume 878 594-597 doi: 10.1111/j.1749-6632.1999.tb07737.x
Billinghurst RC, O'Brien K, Poole AR, McIlwraith CW.No abstract available