Subscribe to RSS
DOI: 10.1055/s-0038-1632973
Matrix metalloproteinase and tissue inhibitor of metalloproteinase in serum and synovial fluid of osteoarthritic dogs
Publication History
Received
24 February 2005
Accepted
25 June 2005
Publication Date:
08 February 2018 (online)
Summary
To better understand the mechanisms responsible for the pathological processes of osteoarthritis (OA) and to potentially identify a profile of changes that could be predictive of early OA, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the synovial fluid and serum of normal and osteoarthritic dogs were examined. The concentration of MMP-1 in the synovial fluid of osteoarthritic dogs (0.62 ± 0.16), as measured by densitometry, was significantly higher than that found in control dogs (0.42 ± 0.19) (P = 0.03). The concentration of MMP-1 in the serum of osteoarthritic dogs (0.74 ± 0.16) was significantly less than that found in control dogs (0.87 ± 0.08) (P = 0.05). The concentration of TIMP-2 in the synovial fluid of osteoarthritic dogs (46.2 ± 21.9 ng/ml) was significantly less than that of control dogs (122.0 ± 66.5 ng/ml) (P = 0.009). The concentration of TIMP-2 in the serum of osteoarthritic dogs (116.2 ± 43.1 ng/ml) was not significantly different than that of control dogs (95.1 ± 94.4 ng/ml) (P = 0.554). In addition, a phospho-tyrosine immunoprecipitation and mass spectrometry were used to isolate and identify interferonalpha in canine synovial fluid.
* Presented at the annual scientific meeting of the American College of Veterinary Surgeons, Denver, CO, USA, October 2004.
-
References
- 1 Aranapakam V, Davis JM, Grosu GT. et al. Synthesis and structure – Active relationship of N-substituted 4-arysulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metallo-proteinase inhibitors for the treatment of osteoarthritis. J Med Chem 2003; 46: 2376-96.
- 2 Birkedal-Hansen H, Moore WG, Bodden MK. et al. Matrix metalloproteinases: A review. Crit Rev in Oral Biol and Med 1993; 4: 197-250.
- 3 Byron CR, Orth MW, Venta PJ. et al. Influence of glucosamine on matrix metalloproteinase expression and activity in lipopolysaccharide-stimulated equine chondrocytes. Am JVet Res 2003; 64: 666-71.
- 4 Catterall JB, Cawston TE. Assay of MMPs and MMP inhibitors: Bioassays and immunoassays applicable to cell culture medium, serum, and synovial fluid. MethodsMol Biol 2003; 225: 353-64.
- 5 Clark IM, Powell LK, Ramsey S. et al. The measurement of collagenase, tissue inhibitor of metalloproteinase (TIMP), and collagenase-TIMP complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 1993; 36: 372-9.
- 6 Clegg PD, Coughlan AR, Carter SD. Equine TIMP-1 and TIMP-2: identification, activity and cellular sources. EqVetJ 1998; 30: 416-23.
- 7 Dean DD, Martel-Pelletier J, Pelletier JP. et al. Evidence for metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest 1989; 84: 678-85.
- 8 Docherty AJ, O'Connell J, Crabbe T. et al. The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseases. Trends Biotechnol 1992; 10: 200-7.
- 9 Fox DB, Cook JL. Synovial fluid markers of osteoarthritis in dogs. J Am Vet Med Assoc 2001; 219: 756-61.
- 10 Gamero AM, Larner AC. Vanadate facilitates interferon alpha-mediated apoptosis that is dependent on the Jak/Stat pathway. J Biol Chem 2001; 276: 13547-53.
- 11 Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum 2000; 43: 1916-26.
- 12 Hedbom E, Hauselmann HJ. Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation. Cell Mol Life Sci 2002; 59: 45-53.
- 13 Hegemann N, Kohn B, Brunnberg L. et al. Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders. Osteoarthritis Cartilage 2002; 10: 714-21.
- 14 Hegemann N, Wondimu A, Ullrich K. et al. Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis. Vet Immunol Immunopathol 2003; 91: 199-204.
- 15 Johnston SA. Osteoarthritis; Joint anatomy, physiology, and pathobiology. Vet Clin N Am 1997; 27: 699-723.
- 16 Lee T, Sumpio BE. Cell signalling in vascular cells exposed to cyclic strain: The emerging role of protein phosphatases. Biotechnol Applied Biochem 2004; 39: 129-39.
- 17 Lohmander LS, Hoerrner LA, Lark MW. Metalloproteinases, tissue inhibitor, and proteoglycan fragments in knee synovial fluid in human osteoarthritis. Arthritis Rheum 1993; 36: 181-9.
- 18 MacNaul KL, Chartrain N, Lark M. et al. Discoordinate expression of stromelysin, collagenase, and tissue inhibitor of metalloproteinases-1 in rheumatoid human synovial fibroblasts. J Biol Chem 1990; 265: 17238-45.
- 19 Manicourt DH, Fujimoto N, Obata K. et al. Serum levels of collagenase, stromelysin-1, and TIMP-1. Arthritis Rheum 1994; 37: 1774-83.
- 20 Martel-Pelletier J. Pathophysiology of Osteoarthritis. Osteoarthritis Cartilage 1999; 7: 371-3.
- 21 Martel-Pelletier J, McCollum R, Fujimoto N. et al. Excess ofmetalloprotease over tissue inhibitor of metalloproteinase may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest 1994; 70: 807-15.
- 22 Nagase H, Woessner JF. Matrix Metalloproteinases. J Biol Chem 1999; 274: 21491-4.
- 23 Pelletier JP, Martel-Pelletier J. The Novartis-ILAR Rheumatology Prize 2001 Osteoarthritis: from molecule to man. Arthritis Res 2002; 4: 13-9.
- 24 Ray A, Kuroki K, Cook JL. et al. Induction of matrix metalloprotein 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis. Arthritis Rheum 2003; 48: 134-45.
- 25 Romerio F, Riva A, Zella D. Interferon-alpha2b reduces phosphorylation and activity of MEK and ERK through a Ras/Raf-independent mechanism. Brit JCancer 2000; 83: 532-8.
- 26 Rorvik AM, Grondahl AM. Markers of osteoarthritis: A review of the literature. Vet Surg 1995; 24: 255-62.
- 27 Thyrell L, Hjortsberg L, Arulampalam V. et al. Interferon alpha-induced apoptosis in tumour cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signalling pathway. J Biol Chem 2004; 279: 24152-62.
- 28 Todhunter RJ, Yeager AE, Freeman KP. et al. Keratin sulphate as amarker of articular cartilage catabolism and joint treatment in ponies. Am J Vet Res 1993; 54: 1007-6.
- 29 Torpey N, Maher SE, Bothwell AL. et al. Interferon alpha butnotinterleukin 12 activates STAT4 signalling in human vascular endothelial cells. J Biol Chem 2004; 279: 26789-96.
- 30 Vaalamo M, Leivo T, Saarialho-Kere U. Differential expression of tissue inhibitors ofmatrix metalloproteinases (TIMP-1, -2, -3, -4) in normal and aberrant wound healing. Hum Pathol 1999; 30: 795-802.
- 31 Volk SW, Kapatkin AS, Haskins ME. et al. Gelatinase activity in synovial fluid and synovium obtained from healthy and osteoarthritic joints of dogs. Am JVet Res 2003; 64: 1225-33.
- 32 Winyard PG. Inflammation protocols Key stages in the acute inflammatory response and their relevance as therapeutic targets. Methods Mol Biol 2003; 225: 3-5.