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Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis

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Abstract

This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.

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References

  1. Murphy G, Knauper V, Atkinson S, Butler G, English W, Hutton M et al (2002) Matrix metalloproteinases in arthritic disease. Arthritis Res 4(Suppl 3):S39–S49

    Article  PubMed  Google Scholar 

  2. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543

    Article  PubMed  CAS  Google Scholar 

  3. Weber AJ, De Bandt M (2000) Angiogenesis: general mechanisms and implications for rheumatoid arthritis. Joint Bone Spine 67(5):366–383

    PubMed  CAS  Google Scholar 

  4. Burbridge MF, Coge F, Galizzi JP, Boutin JA, West DC, Tucker GC (2002) The role of the matrix metalloproteinases during in vitro vessel formation. Angiogenesis 5(3):215–226

    Article  PubMed  CAS  Google Scholar 

  5. Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D et al (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93(3):411–422

    Article  PubMed  CAS  Google Scholar 

  6. Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14(2):163–176

    PubMed  Google Scholar 

  7. Zijlstra A, Aimes RT, Zhu D, Regazzoni K, Kupriyanova T, Seandel M et al (2004) Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). J Biol Chem 279(26):27633–27645

    Article  PubMed  CAS  Google Scholar 

  8. Netzel-Arnett S, Mitola DJ, Yamada SS, Chrysovergis K, Holmbeck K, Birkedal-Hansen H et al (2002) Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity. J Biol Chem 277(47):45154–45161

    Article  PubMed  CAS  Google Scholar 

  9. Kim KS, Park EK, Ju SM, Jung HS, Bang JS, Kim C et al (2007) Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes. Arthritis Res Ther 9(4):R80

    Article  PubMed  Google Scholar 

  10. Bouis D, Kusumanto Y, Meijer C, Mulder NH, Hospers GA (2006) A review on pro- and anti-angiogenic factors as targets of clinical intervention. Pharmacol Res 53(2):89–103

    Article  PubMed  CAS  Google Scholar 

  11. Wang H, Keiser JA (1998) Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res 83(8):832–840

    PubMed  CAS  Google Scholar 

  12. Fraser A, Fearon U, Reece R, Emery P, Veale DJ (2001) Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis. Arthritis Rheum 44(9):2024–2028

    Article  PubMed  CAS  Google Scholar 

  13. Goldbach-Mansky R, Lee JM, Hoxworth JM, Smith D II, Duray P, Schumacher RH Jr et al (2000) Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis. Arthritis Res 2(2):145–153

    Article  PubMed  CAS  Google Scholar 

  14. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2(10):737–744

    Article  PubMed  CAS  Google Scholar 

  15. Heilpern AJ, Wertheim W, He J, Perides G, Bronson RT, Hu LT (2009) Matrix metalloproteinase 9 plays a key role in lyme arthritis but not in dissemination of Borrelia burgdorferi. Infect Immun 77(7):2643–2649

    Article  PubMed  CAS  Google Scholar 

  16. Itoh T, Matsuda H, Tanioka M, Kuwabara K, Itohara S, Suzuki R (2002) The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J Immunol 169(5):2643–2647

    PubMed  CAS  Google Scholar 

  17. Sang QX (1998) Complex role of matrix metalloproteinases in angiogenesis. Cell Res 8(3):171–177

    PubMed  CAS  Google Scholar 

  18. Tchetverikov I, Ronday HK, Van El B, Kiers GH, Verzijl N, TeKoppele JM et al (2004) MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis. Ann Rheum Dis 63(7):881–883

    Article  PubMed  CAS  Google Scholar 

  19. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K et al (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 59(6):455–461

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a research grant from the Kyung Hee University in 2009 (KHU-20100134).

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Correspondence to Kyoung Soo Kim.

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Kim, K.S., Choi, H.M., Lee, YA. et al. Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis. Rheumatol Int 31, 543–547 (2011). https://doi.org/10.1007/s00296-010-1592-1

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  • DOI: https://doi.org/10.1007/s00296-010-1592-1

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