Table of Contents
ISRN Dermatology
Volume 2013 (2013), Article ID 630620, 7 pages
http://dx.doi.org/10.1155/2013/630620
Review Article

Angiogenic and Inflammatory Properties of Psoriatic Arthritis

Department of Dermatology, Fukushima Medical University, Fukushima 960-1295, Japan

Received 22 April 2013; Accepted 15 May 2013

Academic Editors: G. Chodorowska, F. Guarneri, C.-C. Lan, M. Murakami, E. Pasmatzi, and W. Vanscheidt

Copyright © 2013 Toshiyuki Yamamoto. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. L. Boyle and A. Kavanaugh, “The pathobiology of psoriatic synovium,” Current Opinion in Rheumatology, vol. 20, no. 4, pp. 404–407, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. A. W. R. Van Kuijk and P. P. Tak, “Synovitis in psoriatic arthritis: immunohistochemistry, comparisons with rheumatoid arthritis, and effects of therapy,” Current Rheumatology Reports, vol. 13, no. 4, pp. 353–359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Yamamoto, “Psoriatic arthritis: from a dermatological perspective,” European Journal of Dermatology, vol. 21, no. 5, pp. 660–666, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. E. Kruithof, D. Baeten, L. De Rycke et al., “Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis,” Arthritis Research & Therapy, vol. 7, no. 3, pp. R569–R580, 2005. View at Google Scholar · View at Scopus
  5. R. A. Chua and J. L. Arbiser, “The role of angiogenesis in the pathogenesis of psoriasis,” Autoimmunity, vol. 42, no. 7, pp. 574–579, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. R. Heidenreich, M. Röcken, and K. Ghoreschi, “Angiogenesis drives psoriasis pathogenesis,” International Journal of Experimental Pathology, vol. 90, no. 3, pp. 232–248, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Canavese, F. Altruda, T. Ruzicka, and J. Schauber, “Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis—a possible target for novel therapies?” Journal of Dermatological Science, vol. 58, no. 3, pp. 171–176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Ancelin, S. Chollet-Martin, M. A. Hervé, C. Legrand, J. El Benna, and M. Perrot-Applanat, “Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism,” Laboratory Investigation, vol. 84, no. 4, pp. 502–512, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. C. Rosenberger, C. Solovan, A. D. Rosenberger et al., “Upregulation of hypoxia-inducible factors in normal and psoriatic skin,” Journal of Investigative Dermatology, vol. 127, no. 10, pp. 2445–2452, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Detmar, L. F. Brown, M. P. Schön et al., “Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice,” Journal of Investigative Dermatology, vol. 111, no. 1, pp. 1–6, 1998. View at Publisher · View at Google Scholar · View at Scopus
  11. Y. Xia, B. Li, D. Hylton, M. Detmar, G. D. Yancopoulos, and J. S. Rudge, “Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis,” Blood, vol. 102, no. 1, pp. 161–168, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. D. Voskas, N. Jones, P. Van Slyke et al., “A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice,” American Journal of Pathology, vol. 166, no. 3, pp. 843–855, 2005. View at Google Scholar · View at Scopus
  13. T. P. Singh, M. P. Schön, K. Wallbrecht, A. Gruber-Wackernagel, X.-J. Wang, and P. Wolf, “Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis,” PLOS ONE, vol. 8, no. 1, Article ID e51752, 2013. View at Google Scholar
  14. J. R. Zibert, K. Wallbrecht, M. Schön et al., “Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions,” Journal of Clinical Investigation, vol. 121, no. 1, pp. 410–421, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Abe, S. Yamagishi, Y. Fujita et al., “Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis,” Journal of Dermatological Science, vol. 57, no. 3, pp. 183–191, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. P. J. Costello, R. J. Winchester, S. A. Curran et al., “Psoriatic arthritis joint fluids are characterized by CD8 and CD4 T cell clonal expansions that appear antigen driven,” Journal of Immunology, vol. 166, no. 4, pp. 2878–2886, 2001. View at Google Scholar · View at Scopus
  17. T. Yamamoto, H. Yokozeki, and K. Nishioka, “Clinical analysis of 21 patients with psoriasis arthropathy,” Journal of Dermatology, vol. 32, no. 2, pp. 84–90, 2005. View at Google Scholar · View at Scopus
  18. L. Borgato, A. Puccetti, R. Beri et al., “The T cell receptor repertoire in psoriatic synovitis is restricted and T lymphocytes expressing the same TCR are present in joint and skin lesions,” Journal of Rheumatology, vol. 29, no. 9, pp. 1914–1919, 2002. View at Google Scholar · View at Scopus
  19. E. L. Ross, D. D'Cruz, and W. J. W. Morrow, “Localized monocyte chemotactic protein-1 production correlates with T cell infiltration of synovium in patients with psoriatic arthritis,” Journal of Rheumatology, vol. 27, no. 10, pp. 2432–2443, 2000. View at Google Scholar · View at Scopus
  20. J. D. Cañete, B. Santiago, T. Cantaert et al., “Ectopic lymphoid neogenesis in psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 66, no. 6, pp. 720–726, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. H. A. Flytlie, M. Hvid, E. Lindgreen et al., “Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis,” Cytokine, vol. 49, no. 1, pp. 24–29, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Partsch, E. Wagner, B. F. Leeb, H. Bröll, A. Dunky, and J. S. Smolen, “T cell derived cytokines in psoriatic arthritis synovial fluids,” Annals of the Rheumatic Diseases, vol. 57, no. 11, pp. 691–693, 1998. View at Google Scholar · View at Scopus
  23. A. W. R. Van Kuijk, P. Reinders-Blankert, T. J. M. Smeets, B. A. C. Dijkmans, and P. P. Tak, “Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment,” Annals of the Rheumatic Diseases, vol. 65, no. 12, pp. 1551–1557, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Di Cesare, P. Di Meglio, and F. O. Nestle, “The IL-23Th17 axis in the immunopathogenesis of psoriasis,” Journal of Investigative Dermatology, vol. 129, no. 6, pp. 1339–1350, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Wolk, H. S. Haugen, W. Xu et al., “IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not,” Journal of Molecular Medicine, vol. 87, no. 5, pp. 523–536, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Zheng, D. M. Danilenko, P. Valdez et al., “Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis,” Nature, vol. 445, no. 7128, pp. 648–651, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. J. R. Chan, W. Blumenschein, E. Murphy et al., “IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis,” Journal of Experimental Medicine, vol. 203, no. 12, pp. 2577–2587, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. M. N. Hedrick, A. S. Lonsdorf, A. Shirakawa et al., “CCR6 is required for IL-23-induced psoriasis-like inflammation in mice,” Journal of Clinical Investigation, vol. 119, no. 8, pp. 2317–2329, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Kopp, P. Lenz, C. Bello-Fernandez, R. A. Kastelein, T. S. Kupper, and G. Stingl, “IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity,” Journal of Immunology, vol. 170, no. 11, pp. 5438–5444, 2003. View at Google Scholar · View at Scopus
  30. C. L. Danning, G. G. Illei, C. Hitchon, M. R. Greer, D. T. Boumpas, and I. B. McInnes, “Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis,” Arthritis & Rheumatism, vol. 43, no. 6, pp. 1244–1256, 2000. View at Google Scholar
  31. D. Baeten, E. Kruithof, L. De Rycke et al., “Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy,” Arthritis Research & Therapy, vol. 7, no. 2, pp. R359–R369, 2005. View at Google Scholar · View at Scopus
  32. L. C. Zaba, I. Cardinale, P. Gilleaudeau et al., “Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses,” Journal of Experimental Medicine, vol. 204, no. 13, pp. 3183–3194, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. S. L. Jongbloed, M. C. Lebre, A. R. Fraser et al., “Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis,” Arthritis Research & Therapy, vol. 8, no. 1, article R15, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Wang, E. Lee, M. A. Lowes et al., “Prominent production of IL-20 by CD68+/CD11c+ Myeloid-derived cells in psoriasis: gene regulation and cellular effects,” Journal of Investigative Dermatology, vol. 126, no. 7, pp. 1590–1599, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Guttman-Yassky, M. A. Lowes, J. Fuentes-Duculan et al., “Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis,” Journal of Immunology, vol. 181, no. 10, pp. 7420–7427, 2008. View at Google Scholar · View at Scopus
  36. R. Lande, E. Giacomini, B. Serafini et al., “Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis,” Journal of Immunology, vol. 173, no. 4, pp. 2815–2824, 2004. View at Google Scholar · View at Scopus
  37. F. O. Nestle and M. Gilliet, “Defining upstream elements of psoriasis pathogenesis: an emerging role for interferon α,” Journal of Investigative Dermatology, vol. 125, no. 5, pp. 14–15, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. F. O. Nestle, C. Conrad, A. Tun-Kyi et al., “Plasmacytoid predendritic cells initiate psoriasis through interferon-α production,” Journal of Experimental Medicine, vol. 202, no. 1, pp. 135–143, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. J. M. Curtsinger, J. O. Valenzuela, P. Agarwal, D. Lins, and M. F. Mescher, “Cutting edge: type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation,” Journal of Immunology, vol. 174, no. 8, pp. 4465–4469, 2005. View at Google Scholar · View at Scopus
  40. R. Koczulla, G. Von Degenfeld, C. Kupatt et al., “An angiogenic role for the human peptide antibiotic LL-37/hCAP-18,” Journal of Clinical Investigation, vol. 111, no. 11, pp. 1665–1672, 2003. View at Google Scholar · View at Scopus
  41. J. Wenzel, E. Wörenkämper, S. Freutel et al., “Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus,” Journal of Pathology, vol. 205, no. 4, pp. 435–442, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. T. Yamamoto, M. Matsuuchi, K. Watanabe, I. Katayama, and K. Nishioka, “Mast cells in the synovium of patients with psoriasis arthropathy,” Dermatology, vol. 195, no. 1, pp. 73–74, 1997. View at Google Scholar · View at Scopus
  43. L. M. Klein, R. M. Lavker, W. L. Matis, and G. F. Murphy, “Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 22, pp. 8972–8976, 1989. View at Publisher · View at Google Scholar · View at Scopus
  44. L. J. Walsh, G. Trinchieri, H. A. Waldorf, D. Whitaker, and G. F. Murphy, “Human dermal mast cells contain and release tumor necrosis factor α, which induces endothelial leukocyte adhesion molecule 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 10, pp. 4220–4224, 1991. View at Google Scholar · View at Scopus
  45. R. J. Reece, J. D. Canete, W. J. Parsons, P. Emery, and D. J. Veale, “Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis,” Arthritis & Rheumatism, vol. 42, no. 7, pp. 1481–1484, 1999. View at Google Scholar
  46. U. Fearon, K. Griosios, A. Fraser et al., “Angiopoietins, growth factors, and vascular morphology in early arthritis,” Journal of Rheumatology, vol. 30, no. 2, pp. 260–268, 2003. View at Google Scholar · View at Scopus
  47. D. J. Veale, C. Ritchlin, and O. FitzGerald, “Immunopathology of psoriasis and psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 64, no. 2, supplement, pp. ii26–ii29, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Mastroianni, E. Minutilli, A. Mussi et al., “Cytokine profiles during infliximab monotherapy in psoriatic arthritis,” British Journal of Dermatology, vol. 153, no. 3, pp. 531–536, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. P. Cordiali-Fei, E. Trento, G. D'Agosto et al., “Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions,” Annals of the New York Academy of Sciences, vol. 1110, pp. 578–589, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. S. J. Leibovich, P. J. Polverini, H. M. Shepard, D. M. Wiseman, V. Shively, and N. Nuseir, “Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α,” Nature, vol. 329, no. 6140, pp. 630–632, 1987. View at Google Scholar · View at Scopus
  51. D. Veale, G. Yanni, S. Rogers, L. Barnes, B. Bresnihan, and O. FitzGerald, “Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis,” Arthritis & Rheumatism, vol. 36, no. 7, pp. 893–900, 1993. View at Google Scholar · View at Scopus
  52. U. Fiedler, Y. Reiss, M. Scharpfenecker et al., “Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation,” Nature Medicine, vol. 12, no. 2, pp. 235–239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. W. Gao, C. Sweeney, C. Walsh et al., “Notch signaling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2,” Annals of Rheumatic Disease, vol. 72, no. 6, pp. 1080–1088, 2013. View at Google Scholar
  54. M. Numasaki, J. Fukushi, M. Ono et al., “Interleukin-17 promotes angiogenesis and tumor growth,” Blood, vol. 101, no. 7, pp. 2620–2627, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. M. S. Doyle, E. S. Collins, O. M. FitzGerald, and S. R. Pennington, “New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis,” Arthritis Research & Therapy, vol. 14, no. 5, article 226, 2012. View at Google Scholar
  56. T. Noordenbos, N. Yeremenko, I. Gofita et al., “Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis,” Arthritis & Rheumatism, vol. 64, no. 1, pp. 99–109, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. L. De Rycke, B. Vandooren, E. Kruithof, F. De Keyser, E. M. Veys, and D. Baeten, “Tumor necrosis factor α blockade treatment down-modulates the increased systemic and local expression of Toll-like receptor 2 and Toll-like receptor 4 in spondylarthropathy,” Arthritis & Rheumatism, vol. 52, no. 7, pp. 2146–2158, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Seibl, T. Birchler, S. Loeliger et al., “Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium,” American Journal of Pathology, vol. 162, no. 4, pp. 1221–1227, 2003. View at Google Scholar · View at Scopus
  59. Q. Zhang, W. Hui, G. J. Litherland et al., “Differential Toll-like receptor-dependent collagenase expression in chondrocytes,” Annals of the Rheumatic Diseases, vol. 67, no. 11, pp. 1633–1641, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Brentano, D. Kyburz, and S. Gay, “Toll-like receptors and rheumatoid arthritis,” Methods in Molecular Biology, vol. 517, pp. 329–343, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. D. Kane, L. E. Jensen, S. Grehan, A. S. Whitehead, B. Bresnihan, and O. Fitzgerald, “Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis synovial tissue distal and proximal to the cartilage-pannus junction,” Journal of Rheumatology, vol. 31, no. 7, pp. 1274–1280, 2004. View at Google Scholar · View at Scopus
  62. S. M. Sacre, E. Andreakos, S. Kiriakidis et al., “The toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritis,” American Journal of Pathology, vol. 170, no. 2, pp. 518–525, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Abdollahi-Roodsaz, L. A. B. Joosten, M. I. Koenders et al., “Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 205–216, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Candia, J. Marquez, C. Hernandez, A. H. Zea, and L. R. Espinoza, “Toll-like receptor-2 expression is upregulated in antigen-presenting cells from patients with psoriatic arthritis: a pathogenic role for innate immunity?” Journal of Rheumatology, vol. 34, no. 2, pp. 374–379, 2007. View at Google Scholar · View at Scopus
  65. B. Raffeiner, C. Dejaco, C. Duftner et al., “Between adaptive and innate immunity: TLR4-mediated perforin production by CD28null T-helper cells in ankylosing spondylitis,” Arthritis Research & Therapy, vol. 7, no. 6, pp. R1412–R1420, 2005. View at Google Scholar · View at Scopus
  66. B. Beutler, “Inferences, questions and possibilities in Toll-like receptor signalling,” Nature, vol. 430, no. 6996, pp. 257–263, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Costello, B. Bresnihan, C. O'Farrelly, and O. Fitzgerald, “Predominance of CD8+ T lymphocytes in psoriatic arthritis,” Journal of Rheumatology, vol. 26, no. 5, pp. 1117–1124, 1999. View at Google Scholar · View at Scopus
  68. I. Goldstein, A. J. Simon, S. B. Horin et al., “Synovial VLA-1+ T cells display an oligoclonal and partly distinct repertoire in rheumatoid and psoriatic arthritis,” Clinical Immunology, vol. 128, no. 1, pp. 75–84, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. G. Partsch, G. Steiner, B. F. Leeb, A. Dunky, H. Bröll, and J. S. Smolen, “Highly increased levels of tumor necrosis factor-α and other proinflammatory cytokines in psoriatric arthritis synovial fluid,” Journal of Rheumatology, vol. 24, no. 3, pp. 518–523, 1997. View at Google Scholar · View at Scopus
  70. G. Partsch, E. Wagner, B. F. Leeb, A. Dunky, G. Steiner, and J. S. Smolen, “Upregulation of cytokine receptors sTNF-R55, STNF-R75, and sIL-2r in psoriatic arthritis synovial fluid,” Journal of Rheumatology, vol. 25, no. 1, pp. 105–110, 1998. View at Google Scholar · View at Scopus
  71. A. Mitra, S. K. Raychaudhuri, and S. P. Raychaudhuri, “Functional role of IL-22 in psoriatic arthritis,” Arthritis Research & Therapy, vol. 14, article R65, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Sabat, S. Philipp, C. Höflich et al., “Immunopathogenesis of psoriasis,” Experimental Dermatology, vol. 16, no. 10, pp. 779–798, 2007. View at Google Scholar
  73. A. Spadaro, T. Rinaldi, V. Riccieri, G. Valesini, and E. Taccari, “Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 61, no. 2, pp. 174–176, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Wolk, E. Witte, E. Wallace et al., “IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis,” European Journal of Immunology, vol. 36, no. 5, pp. 1309–1323, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. T. Loos, L. Dekeyzer, S. Struyf et al., “TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis,” Laboratory Investigation, vol. 86, no. 9, pp. 902–916, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Fraser, U. Fearon, R. Reece, P. Emery, and D. J. Veale, “Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis,” Arthritis & Rheumatism, vol. 44, no. 9, pp. 2024–2028, 2001. View at Google Scholar