Osteoarthritis and Cartilage
Volume 18, Issue 9 , Pages 1109-1116 , September 2010

Identifying the human aggrecanase

  • A.J. Fosang

      Affiliations

    • Corresponding Author InformationAddress correspondence and reprint requests to: University of Melbourne, Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Australia.
  • ,
  • F.M. Rogerson

Received 9 April 2010 ,Accepted 4 June 2010.

References 

  1. Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R, et al. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science. 1999;284:1664–1666
  2. Abbaszade I, Liu RQ, Yang F, Rosenfeld SA, Ross OH, Link JR, et al. Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family. J Biol Chem. 1999;274:23443–23450
  3. Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, et al. Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis. Arthritis Rheum. 2008;58:435–441
  4. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, et al. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum. 2007;56:575–585
  5. Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E, Aigner T. Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum. 2002;46:2648–2657
  6. Moulharat N, Lesur C, Thomas M, Rolland-Valognes G, Pastoureau P, Anract P, et al. Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro. Osteoarthritis Cartilage. 2004;12:296–305
  7. Naito S, Shiomi T, Okada A, Kimura T, Chijiiwa M, Fujita Y, et al. Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage. Pathol Int. 2007;57:703–711
  8. Yatabe T, Mochizuki S, Takizawa M, Chijiiwa M, Okada A, Kimura T, et al. Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes. Ann Rheum Dis. 2009;
  9. Young DA, Lakey RL, Pennington CJ, Jones D, Kevorkian L, Edwards DR, et al. Histone deacetylase inhibitors modulate metalloproteinase gene expression in chondrocytes and block cartilage resorption. Arthritis Res Ther. 2005;7:R503–R512
  10. Sawaji Y, Hynes J, Vincent T, Saklatvala J. Fibroblast growth factor 2 inhibits induction of aggrecanase activity in human articular cartilage. Arthritis Rheum. 2008;58:3498–3509
  11. Fosang AJ, Rogerson FM, East CJ, Stanton H. ADAMTS-5: the story so far. Eur Cell Mater. 2008;15:11–26
  12. Aigner T, Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, et al. Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum. 2006;54:3533–3544
  13. Aigner T, Zien A, Gehrsitz A, Gebhard PM, McKenna L. Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology. Arthritis Rheum. 2001;44:2777–2789
  14. Sato T, Konomi K, Yamasaki S, Aratani S, Tsuchimochi K, Yokouchi M, et al. Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage. Arthritis Rheum. 2006;54:808–817
  15. Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004;50:131–141
  16. Plaas A, Osborn B, Yoshihara Y, Bai Y, Bloom T, Nelson F, et al. Aggrecanolysis in human osteoarthritis: confocal localization and biochemical characterization of ADAMTS5-hyaluronan complexes in articular cartilages. Osteoarthritis Cartilage. 2007;15:719–734
  17. Malfait A-M, Liu R-Q, Ijiri K, Komiya S, Tortorella MD. Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage. J Biol Chem. 2002;277:22201–22208
  18. Roach HI, Yamada N, Cheung KS, Tilley S, Clarke NM, Oreffo RO, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum. 2005;52:3110–3124
  19. Dieppe P, Kirwan J. The localization of osteoarthritis. Br J Rheumatol. 1994;33:201–203
  20. Yamanishi Y, Boyle DL, Clark M, Maki RA, Tortorella MD, Arner EC, et al. Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol. 2002;168:1405–1412
  21. Vankemmelbeke MN, Holen I, Wilson AG, Ilic MZ, Handley CJ, Kelner GS, et al. Expression and activity of ADAMTS-5 in synovium. Eur J Biochem. 2001;268:1259–1268
  22. Vankemmelbeke MN, Ilic MZ, Handley CJ, Knight CG, Buttle DJ. Coincubation of bovine synovial or capsular tissue with cartilage generates a soluble “aggrecanase” activity. Biochem Biophys Res Commun. 1999;255:686–691
  23. Zielinska B, Killian M, Kadmiel M, Nelsen M, Haut Donahue TL. Meniscal tissue explants response depends on level of dynamic compressive strain. Osteoarthritis Cartilage. 2009;17:754–760
  24. Ilic MZ, Vankemmelbeke MN, Holen I, Buttle DJ, Clem RH, Handley CJ. Bovine joint capsule and fibroblasts derived from joint capsule express aggrecanase activity. Matrix Biol. 2000;19:257–265
  25. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther. 2006;8:R187
  26. Davidson RK, Waters JG, Kevorkian L, Darrah C, Cooper A, Donell ST, et al. Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage. Arthritis Res Ther. 2006;8:R124
  27. Wainwright SD, Bondeson J, Hughes CE. An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. Matrix Biol. 2006;25:317–320
  28. Okabe T, Ohmori Y, Tanigami A, Hishigaki H, Suzuki Y, Sugano S, et al. Detection of gene expression in synovium of patients with osteoarthritis using a random sequencing method. Acta Orthop. 2007;78:687–692
  29. East CJ, Rogerson FM, Lawlor KE, Stanton H, Fosang AJ. ADAMTS-5 activity in synovial fibroblasts is different to chondrocytes. Trans Orthop Res Soc. 2007;576;San Diego
  30. Van Beuningen HM, Glansbeek HL, van der Kraan PM, Van Den Berg WB. Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage. 1998;6:306–317
  31. van Lent PL, Grevers LC, Blom AB, Arntz OJ, van de Loo FA, van der Kraan P, et al. Stimulation of chondrocyte-mediated cartilage destruction by S100A8 in experimental murine arthritis. Arthritis Rheum. 2008;58:3776–3787
  32. Thirunavukkarasu K, Pei Y, Moore TL, Wang H, Yu XP, Geiser AG, et al. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines. Biochem Biophys Res Commun. 2006;345:197–204
  33. Thirunavukkarasu K, Pei Y, Wei T. Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter. Mol Biol Rep. 2007;
  34. Fushimi K, Troeberg L, Nakamura H, Lim NH, Nagase H. Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity. J Biol Chem. 2008;283:6706–6716
  35. Amaral PP, Dinger ME, Mercer TR, Mattick JS. The eukaryotic genome as an RNA machine. Science. 2008;319:1787–1789
  36. Iliopoulos D, Malizos KN, Oikonomou P, Tsezou A. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS ONE. 2008;3:e3740
  37. Miyaki S, Nakasa T, Otsuki S, Grogan SP, Higashiyama R, Inoue A, et al. MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses. Arthritis Rheum. 2009;60:2723–2730
  38. Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, Yokoyama S, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 2010;24
  39. Tardif G, Hum D, Pelletier JP, Duval N, Martel-Pelletier J. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord. 2009;10:148
  40. Cheung KS, Hashimoto K, Yamada N, Roach HI. Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatol Int. 2009;29:525–534
  41. da Silva MA, Yamada N, Clarke NM, Roach HI. Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res. 2009;27:593–601
  42. Roman-Gomez J, Jimenez-Velasco A, Agirre X, Prosper F, Heiniger A, Torres A. Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis. J Clin Oncol. 2005;23:7043–7049
  43. Flannery CR, Little CB, Hughes CE, Caterson B. Expression of ADAMTS homologues in articular cartilage. Biochem Biophys Res Commun. 1999;260:318–322
  44. Pratta MA, Scherle PA, Yang G, Liu RQ, Newton RC. Induction of aggrecanase 1 (ADAM-TS4) by interleukin-1 occurs through activation of constitutively produced protein. Arthritis Rheum. 2003;48:119–133
  45. Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE. Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a cys73 active-site zinc complex in latency and a “cysteine switch” mechanism for activation. Proc Natl Acad Sci USA. 1990;87:364–368
  46. Gonzales PE, Solomon A, Miller AB, Leesnitzer MA, Sagi I, Milla ME. Inhibition of the tumor necrosis factor-alpha-converting enzyme by its pro domain. J Biol Chem. 2004;279:31638–31645
  47. Buckley CA, Rouhani FN, Kaler M, Adamik B, Hawari FI, Levine SJ. Amino-terminal TACE prodomain attenuates TNFR2 cleavage independently of the cysteine switch. Am J Physiol Lung Cell Mol Physiol. 2005;288:L1132–L1138
  48. Tortorella MD, Arner EC, Hills R, Gormley J, Fok K, Pegg L, et al. ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms. Arch Biochem Biophys. 2005;444:34–44
  49. Wang P, Tortorella M, England K, Malfait AM, Thomas G, Arner EC, et al. Proprotein convertase furin interacts with and cleaves pro-ADAMTS4 (aggrecanase-1) in the trans-Golgi network. J Biol Chem. 2004;279:15434–15440
  50. Longpre JM, McCulloch DR, Koo BH, Alexander JP, Apte SS, Leduc R. Characterization of proADAMTS5 processing by proprotein convertases. Int J Biochem Cell Biol. 2009;41:1116–1126
  51. Mayer G, Hamelin J, Asselin MC, Pasquato A, Marcinkiewicz E, Tang M, et al. The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates. J Biol Chem. 2008;283:2373–2384
  52. Malfait AM, Arner EC, Song RH, Alston JT, Markosyan S, Staten N, et al. Proprotein convertase activation of aggrecanases in cartilage in situ. Arch Biochem Biophys. 2008;478:43–51
  53. Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002;3:753–766
  54. Gao G, Plaas A, Thompson VP, Jin S, Zuo F, Sandy JD. ADAMTS4 (aggrecanase-1) activation on the cell surface involves C-terminal cleavage by glycosylphosphatidyl inositol-anchored membrane type 4-matrix metalloproteinase and binding of the activated proteinase to chondroitin sulfate and heparan sulfate on syndecan-1. J Biol Chem. 2004;279:10042–10051
  55. Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR. Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18. Biochim Biophys Acta. 2006;1760:517–524
  56. Flannery CR, Zeng W, Corcoran C, Collins-Racie LA, Chockalingam PS, Hebert T, et al. Autocatalytic cleavage of ADAMTS-4 (aggrecanase-1) reveals multiple glycosaminoglycan-binding sites. J Biol Chem. 2002;277:42775–42780
  57. Gao G, Westling J, Thompson VP, Howell TD, Gottschall PE, Sandy JD. Activation of the proteolytic activity of ADAMTS4 (aggrecanase-1) by C-terminal truncation. J Biol Chem. 2002;277:11034–11041
  58. Tortorella MD, Liu RQ, Burn T, Newton RC, Arner E. Characterization of human aggrecanase 2 (ADAM-TS5): substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4). Matrix Biol. 2002;21:499–511
  59. Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thogersen IB, Hughes C, et al. Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. J Biol Chem. 2007;282:18294–18306
  60. Kashiwagi M, Enghild JJ, Gendron C, Hughes C, Caterson B, Itoh Y, et al. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. J Biol Chem. 2004;279:10109–10119
  61. Hashimoto G, Shimoda M, Okada Y. ADAMTS4 (aggrecanase-1) interaction with the C-terminal domain of fibronectin inhibits proteolysis of aggrecan. J Biol Chem. 2004;279:32483–32491
  62. Wang LW, Leonhard-Melief C, Haltiwanger RS, Apte SS. Post-translational modification of thrombospondin type-1 repeats in ADAMTS-like 1/punctin-1 by C-mannosylation of tryptophan. J Biol Chem. 2009;284:30004–30015
  63. Apte SS. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem. 2009;284:31493–31497
  64. Pratta MA, Tortorella MD, Arner EC. Age-related changes in aggrecan glycosylation affect cleavage by aggrecanase. J Biol Chem. 2000;275:39096–39102
  65. Tortorella M, Pratta M, Liu RQ, Abbaszade I, Ross H, Burn T, et al. The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. J Biol Chem. 2000;275:25791–25797
  66. Poon CJ, Plaas AH, Keene DR, McQuillan DJ, Last K, Fosang AJ. N-linked keratan sulfate in the aggrecan interglobular domain potentiates aggrecanase activity. J Biol Chem. 2005;280:23615–23621
  67. Brown GM, Huckerby TN, Bayliss MT, Nieduszynski IA. Human aggrecan keratan sulfate undergoes structural changes during adolescent development. J Biol Chem. 1998;273:26408–26414
  68. Fosang AJ, Last K, Poon CJ, Plaas AH. Keratan sulphate in the interglobular domain has a microstructure that is distinct from keratan sulphate elsewhere on pig aggrecan. Matrix Biol. 2009;28:53–61
  69. Roughley PJ, Barnett J, Zuo F, Mort JS. Variations in aggrecan structure modulate its susceptibility to aggrecanases. Biochem J. 2003;375:183–189
  70. Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem. 2001;276:12501–12504
  71. Hashimoto G, Aoki T, Nakamura H, Tanzawa K, Okada Y. Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4). FEBS Lett. 2001;494:192–195
  72. Sahebjam S, Khokha R, Mort JS. Increased collagen and aggrecan degradation with age in the joints of Timp3(−/−) mice. Arthritis Rheum. 2007;56:905–909
  73. Yu WH, Yu S, Meng Q, Brew K, Woessner JF. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J Biol Chem. 2000;275:31226–31232
  74. Wayne GJ, Deng SJ, Amour A, Borman S, Matico R, Carter HL, et al. TIMP-3 inhibition of ADAMTS-4 (aggrecanase-1) is modulated by interactions between aggrecan and the C-terminal domain of ADAMTS-4. J Biol Chem. 2007;282:20991–20998
  75. Troeberg L, Fushimi K, Khokha R, Emonard H, Ghosh P, Nagase H. Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases. Faseb J. 2008;
  76. Tortorella MD, Arner EC, Hills R, Easton A, Korte-Sarfaty J, Fok K, et al. Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and represents an endogenous inhibitor of these enzymes. J Biol Chem. 2004;279:17554–17561
  77. Lee NV, Rodriguez-Manzaneque JC, Thai SN, Twal WO, Luque A, Lyons KM, et al. Fibulin-1 acts as a cofactor for the matrix metalloprotease ADAMTS-1. J Biol Chem. 2005;280:34796–34804
  78. McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, et al. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell. 2009;17:687–698
  79. Aspberg A, Adam S, Kostka G, Timpl R, Heineg . Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican. J Biol Chem. 1999;274:20444–20449
  80. Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, et al. Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med. 2009;15:1072–1077
  81. Hughes CE, Caterson B, Fosang AJ, Roughley PJ, Mort JS. Monoclonal antibodies that specifically recognise neo-epitope sequences generated by “aggrecanase” and matrix metalloproteinase cleavage of aggrecan: application to catabolism in situ and in vitro. Biochem J. 1995;305:799–804
  82. Swearingen C, Carpenter J, Siegel R, Brittain I, Dotzlaf J, Durham TB, et al. Development of a novel clinical biomarker assay to detect and quantify aggrecanase-generated aggrecan fragments in human synovial fluid, serum and urine. Osteoarthritis Cartilage. 2010;18:1140–1148
  83. Rogerson FM, Stanton H, East CJ, Golub SB, Tutolo L, Farmer PJ, et al. Evidence of a novel aggrecan-degrading activity in cartilage: studies of mice deficient in both ADAMTS-4 and ADAMTS-5. Arthritis Rheum. 2008;58:1664–1673

PII: S1063-4584(10)00219-0

doi: 10.1016/j.joca.2010.06.014

Osteoarthritis and Cartilage
Volume 18, Issue 9 , Pages 1109-1116 , September 2010