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Proteinases and their Inhibitors in Cartilage and Synovial Fluid Acquired from a Canine Osteoarthritic Model  

Seo, Jae-Won (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Lee, Hae-Beom (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Kim, Nam-Soo (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Lee, Young-Hoon (Institute of Oral Bioscience, School of Dentistry, Chonbuk National University)
Kang, Hyung-Sub (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Kim, In-Shik (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Park, Sang-Youel (Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Publication Information
Journal of Veterinary Clinics / v.26, no.2, 2009 , pp. 144-149 More about this Journal
Abstract
Chondrocytes and synovial fluid derived markers are used to monitor for osteoarthritis(OA). Specific inhibitors, known as tissue inhibitors of metalloproteinases(TIMP), regulate the proteolytic activity of matrix metalloproteinases(MMP). This study investigated whether MMP and TIMP levels were altered in synovial fluid and cartilage following the experimental induction of OA in canines. Twenty mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and the medial collateral ligament as well as a medial meniscectomy. Matrix metalloproteinase-2 and MMP-9 levels were assayed using Western blot and TIMP-2 levels were measured with enzyme-linked immunosorbent assays four weeks after OA induction. Increased MMP-2 expression was observed in chondrocytes isolated from cartilage following OA induction, but MMP-9 expression decreased. Matrix metalloproteinase-2 and MMP-9 levels in synovial fluid from the OA induced joint significantly increased compared to those of the sham group. Tissue inhibitors of metalloproteinase-2 concentrations were higher in chondrocytes from the OA cartilage, yet TIMP-2 remained lower in the synovial fluid of OA. This suggests the elevated release of MMP-9 over MMP-2 into the synovial fluid following the cartilage degradation-related death of chondrocytes after OA. Osteoarthritis can be further deteriorated by increased MMP activity in the synovial fluid because TIMP-2 exist low concentration into the extracellular matrix. As a result, MMP activity, particularly MMP-9 activity, can be useful as a biomarker in diagnosing and monitoring the early stages of canine OA.
Keywords
MMP; TIMP; osteoarthritis; cartilage; synovial fluid;
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1 Green MJ, Gough AK, Devlin J, Smith J, Astin P, Taylor D, Emery P. Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 2003; 42: 83-88   DOI   ScienceOn
2 Pond MJ, Nuki G. Experimentally-induced osteoarthritis in the dog. Ann Rheum Dis 1973; 32: 387-388   DOI   ScienceOn
3 Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH. Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis. Clin Exp Rheumatol 2003; 21: 465-472   PUBMED
4 Rogers J, Shepstone L, Dieppe P. Is osteoarthritis a systemic disorder of bone? Arthritis Rheum 2004; 50: 452-457   DOI   ScienceOn
5 Steffensen B, Wallon UM, Overall CM. Extracellular matrix binding properties of recombinant fibronectin type II-like modules of human 72-kDa gelatinase/type IV collagenase. High affinity binding to native type I collagen but not native type IV collagen. J Biol Chem 1995; 270: 11555-11566   DOI   ScienceOn
6 Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92: 827-839   DOI   ScienceOn
7 Arican M, Carter SD, Bennett D, Ross G, Ayad S. Increased metabolism of collagen VI in canine osteoarthritis. J Comp Pathol 1996; 114: 249-256   DOI   ScienceOn
8 Little C, Smith S, Ghosh P, Bellenger C. Histomorphological and immunohistochemical evaluation of joint changes in a model of osteoarthritis induced by lateral meniscectomy in sheep. J Rheumatol 1997; 24: 2199-2209
9 Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 2000; 59: 455-461   DOI   ScienceOn
10 Dingle JT. Catabolin--a cartilage catabolic factor from synovium. Clin Orthop Relat Res 1981; 219-231   PUBMED
11 Dean DD, Martel-Pelletier J, Pelletier JP, Howell DS, Woessner JF, Jr. Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest 1989; 84: 678-685   DOI   PUBMED   ScienceOn
12 Knauper V, Bailey L, Worley JR, Soloway P, Patterson ML, Murphy G. Cellular activation of proMMP-13 by MT1-MMP depends on the C-terminal domain of MMP-13. FEBS Lett 2002; 532: 127-130   DOI   PUBMED   ScienceOn
13 Lohmander LS. What is the current status of biochemical markers in the diagnosis, prognosis and monitoring of osteoarthritis? Baillieres Clin Rheumatol 1997; 11: 711-726   DOI   PUBMED   ScienceOn
14 Morgan JP, Wind A, Davidson AP. Bone dysplasias in the labrador retriever: a radiographic study. J Am Anim Hosp Assoc 1999; 35: 332-340   DOI   PUBMED
15 Nagase H, Woessner JF, Jr. Matrix metalloproteinases. J Biol Chem 1999; 274: 21491-21494   DOI   PUBMED
16 Rogers J, Shepstone L, Dieppe P. Is osteoarthritis a systemic disorder of bone? Arthritis Rheum 2004; 50: 452-457   DOI   ScienceOn
17 Arican M, Carter SD, Bennett D, May C. Measurement of glycosaminoglycans and keratan sulphate in canine arthropathies. Res Vet Sci 1994; 56: 290-297   DOI   PUBMED   ScienceOn
18 Arican M, Carter SD, Bennett D. Osteocalcin in canine joint diseases. Br Vet J 1996; 152: 411-423   DOI   ScienceOn
19 Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000; 1477: 267-283   DOI   PUBMED   ScienceOn
20 Hegemann N, Wondimu A, Ullrich K, Schmidt MF. Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis. Vet Immunol Immunopathol 2003; 91: 199-204   DOI   ScienceOn
21 Hill CL, Seo GS, Gale D, Totterman S, Gale ME, Felson DT. Cruciate ligament integrity in osteoarthritis of the knee. Arthritis Rheum 2005; 52: 794-799   DOI   ScienceOn
22 Allan JA, Docherty AJ, Barker PJ, Huskisson NS, Reynolds JJ, Murphy G. Binding of gelatinases A and B to type-I collagen and other matrix components. Biochem J 1995; 309 (Pt 1): 299-306   DOI
23 Murphy G, Knauper V, Atkinson S, Butler G, English W, Hutton M, Stracke J, Clark I. Matrix metalloproteinases in arthritic disease. Arthritis Res 2002; 4 Suppl 3: S39-49   DOI
24 Panula HE, Lohmander LS, Ronkko S, Agren U, Helminen HJ, Kiviranta I. Elevated levels of synovial fluid PLA2, stromelysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs. Acta Orthop Scand 1998; 69: 152-158   DOI   PUBMED
25 Ushiyama T, Chano T, Inoue K, Matsusue Y. Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids. Ann Rheum Dis 2003; 62: 108-112   DOI   ScienceOn
26 Hegemann N, Kohn B, Brunnberg L, Schmidt MF. Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders. Osteoarthritis Cartilage 2002; 10: 714-721   DOI   ScienceOn
27 Ishiguro N, Ito T, Obata K, Fujimoto N, Iwata H. Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis. J Rheumatol 1996; 23: 1599-1604   PUBMED