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Role of stromelysin-1 in cartilage metabolism

  • Chapter
Metalloproteinases as Targets for Anti-Inflammatory Drugs

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Stromelysin-1 (MMP-3, EC 3.4.24.17) is a member of the secreted matrix metalloproteinases (MMPs) family. Like other members of this family, stromelysin-1 (SLN-1) is synthesized and secreted as an inactive zymogen [1]. Several proteinases activate this enzyme in vitro,however, the physiological activator has yet to be identified. The expression of SLN-1 is upregulated by pro-inflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor a (TNFα) [2, 3]. Once activated, SLN-1 has the capability to activate other members of the MMP family [4 – 6], as well as degrade several extracellular matrix components [7 – 10]. The activity of SLN-1 is controlled by several natural inhibitors including tissue inhibitors of metalloproteinases (TIMPs) [11] and a2-macroglobulin [11]. Over the last several years, mounting evidence has accumulated to suggest a role for this enzyme in the accelerated cartilage matrix degradation observed in both rheumatoid arthritis (RA) and osteoarthritis (OA). In this review, we will describe some of the data which indicate that SLN-1 may play a role in the cartilage catabolism seen in these diseases and which suggests that this enzyme may be a reasonable target for inhibition as a means to control cartilage degeneration.

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References

  1. Okada Y, Harris ED, Nagase H (1988) The precursor of metalloendopeptidase from human rheumatoid synovial fibroblasts. Purification and mechanisms of activation by endopeptidases and 4-amino-phenylmercuric acetate. Biochem J 254: 731–741

    PubMed  CAS  Google Scholar 

  2. MacNaul KL, Chartrain N, Lark M, Tocci MJ, Hutchinson NI (1990) Discoordinate expression of stromelysin, collagenase, and tissue inhibitor of metalloproteinases-1 in rheumatoid human synovial fibroblasts. Synergistic effects of interleukin-1 and tumor necrosis factor-a on stromelysin expression. J Biol Chem 265: 17238–17245

    PubMed  CAS  Google Scholar 

  3. Goldring MB, Birkhead JR, Suaen L-F, Yamin R, Mizuno S, Glowacki J, Arbiser JL, Apperley JF (1994) Interleukin-lb-modulated gene expression in immortalized human chondrocytes. J Clin Invest 94: 2307–2316

    Article  PubMed  CAS  Google Scholar 

  4. Murphy G, Cockett MI, Stephens PE, Smith BJ, Docherty AJP (1987) Stromelysin is an activator of procollagenase. A study with natural and recombinant enzymes. Biochem J 248:265–268

    PubMed  CAS  Google Scholar 

  5. Miyazaki K, Fuminori U, Funahashi K, Koshikawa N, Yasumitsu H, Umeda M (1992) Activation of TIMP-2/Progelatinase A complex by stromelysin. Biochem and Biophys Res Com 185: 852–859

    Article  CAS  Google Scholar 

  6. Shapiro SD, Fiszar CJ, Broekelmann TJ, Mecham RP, Senior RM, Weigus HG (1995) Activation of the 92-kDa gelatinase by stromelysin and 4-aminophenylmercuric acetate. J Biol Chem 270: 6351–6356

    Article  PubMed  CAS  Google Scholar 

  7. Flannery CR, Lark MW, Sandy JD (1992) Identification of a stromelysin cleavage site within the interglobular domain of human aggrecan: evidence for proteolysis at this site in vivo in human articular cartilage. J Biol Chem 267: 1008–1014

    PubMed  CAS  Google Scholar 

  8. Fosang AJ, Neame PJ, Hardingham TE, Murphy G, Hamilton JA (1991) Cleavage of cartilage proteoglycan between Gl and G2 domains by stromelysins. J Biol Chem 266: 15579–15582

    PubMed  CAS  Google Scholar 

  9. Nguyen Q, Murphy G, Roughley PJ, Mort JS (1989) Degradation of proteoglycan aggregate by a cartilage metalloproteinase: evidence for the involvement of stromelysin in the generation of link protein heterogeneity in situ. Biochem J 259: 61–68

    PubMed  CAS  Google Scholar 

  10. Wu JJ, Lark MW, Chun LE, Eyre DR (1991) Sites of stromelysin cleavage in collagen types II, IX, X and XI of cartilage. J Biol Chem 266: 5625–5628

    PubMed  CAS  Google Scholar 

  11. Murphy G, Koklitis P, Carne AF (1989) Dissociation of tissue inhibitor of metallopro-teinases (TIMP) from enzyme complexes yields a fully active inhibitor. Biochem J 261: 1031–1034

    PubMed  CAS  Google Scholar 

  12. Enghild JJ, Salvesen G, Brew K, Nagase H (1989) Interaction of human rheumatoid synovial collagenase (matrix metalloproteinase-1) and stromelysin (matrix metallopro-teinase-3) with human oc2-macroglobulin and chick ovostatin: binding kinetics and identification of matrix metalloproteinase cleavage sites. J Biol Chem 265: 8779–8785

    Google Scholar 

  13. Aydelotte MB, Kuettner KE (1988) Differences between sub-populations of cultured bovine articular chondocytes I. Morphology and cartilage matrix production. Conn Tis Res 18: 205–222

    Article  CAS  Google Scholar 

  14. Maroudas A (1975) Glycosaminoglycan turn-over in articular cartilage. Philos Trans R Soc Lond B Biol Sci 271(912): 293–313

    Article  PubMed  CAS  Google Scholar 

  15. Okada Y, Shinmei M, Tanaka O, Naka K, Kimura A, Nakanishi I, Bayliss M, Iwata K, Nagase H (1992) Localization of matrix metalloproteinase 3 (stromelysin) in osteo-arthritic cartilage and synovium. Lab Invest 66: 680–690

    PubMed  CAS  Google Scholar 

  16. Ward RV, Hembry RM, Reynolds JJ, Murphy G (1991) The purification of tissue inhibitor of metalloproteinases-2 from its 72 kDa progelatinase complex. Biochem J 278: 179–187

    PubMed  CAS  Google Scholar 

  17. Dean DD, Martel-Pelletier J-P, Pelletier J-P, Howell DS, Woessner JF Jr (1989) Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthrit-ic cartilage. J Clin Invest 84: 678–685

    Article  PubMed  CAS  Google Scholar 

  18. Chin JR, Murphy G, Werb Z (1985) Stromelysin, a connective tissue-degrading metal-loendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates. J Biol Chem 266: 12367–12376

    Google Scholar 

  19. Okada Y, Nagase H, Harris ED Jr (1986) A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue components. Purification and characterization. J Biol Chem 261: 14245–14255

    PubMed  CAS  Google Scholar 

  20. Whitham SE, Murphy G, Angel P, Rhamsdorf HJ, Smith BJ, Lyons A, Harris TJR, Reynolds JJ, Herrlich P, Docherty AJP (1986) Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J 240: 913–916

    PubMed  CAS  Google Scholar 

  21. Hembry RM, Bagga MR, Reynold JJ, Hamblen DL (1995) Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo-and rheumatoid arthritis. Ann Rheum Dis 54: 25–34

    Article  PubMed  CAS  Google Scholar 

  22. Tetlow TC, Wooley DE (1995) Mast cells, cytokines, and metalloproteinases at the rheumatoid lesion: dual immunolocalisation study. Ann Rheum Dis 54: 896–903

    Article  PubMed  CAS  Google Scholar 

  23. Case JP, Lafyatis R, Remmers EF, Kumkumian GK, Wilder RL (1989) Transin/ stromelysin expression in rheumatoid synovium. A transformation-associated metallo-proteinase secreted by phenotypically invasive synoviocytes. Am J Path 135: 1055–1064

    PubMed  CAS  Google Scholar 

  24. Gravallese EM, Darling JM, Ladd AL, Katz JN, Glimcher LH (1991) In situ hybridization studies of stromelysin and collagenase expression in rheumatoid synovium. Arthritis Rheum 34: 1076–1084

    Article  PubMed  CAS  Google Scholar 

  25. Nguyen Q, Mort JS, Roughly PJR (1992) Preferential mRNA expression of prostromelysin relative to procollagenase and in situ localization in human articular cartilage. J Clin Invest 89: 1189–1197

    Article  PubMed  CAS  Google Scholar 

  26. Gunja-Smith Z, Nagase H, Woessner JF Jr (1989) Purification of the neutral proteoglycan-degrading metalloproteinase from human articular cartilage tissue and its identification as stromelysin matrix metalloproteinase-3. Biochem J 258: 115–119

    PubMed  CAS  Google Scholar 

  27. Cooksley S, Hipkiss JB, Tickle SP, Holmesievers E, Docherty AJP, Murphy G, Lawson ADG (1990) Immunoassays for the detection of human collagenase; stromelysin; tissue inhibitor of metalloproteinases (TIMP) and enzyme-inhibitor complexes. Matrix 10: 285–291

    Article  PubMed  CAS  Google Scholar 

  28. Walakovits LA, Moore VL, Bhardwaj N, Gallick GS, Lark MW (1992) Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury. Arthritis Rheum 35: 35–42

    Article  PubMed  CAS  Google Scholar 

  29. Lohmander LS, Hoerrner LA, Lark MW (1993) Metalloproteinases, tissue inhibitor and proteoglycan fragments in knee synovial fluid in human osteoarthritis. Arthritis Rheum 36: 181–189

    Article  PubMed  CAS  Google Scholar 

  30. Yoshihara Y, Obata K, Fujimoto N, Yamashita K, Hayakawa T, Shimmei M (1995) Increased levels of stromelysin-1 and tissue inhibitor of metalloproteinases-1 in sera from patients with rheumatoid arthritis. Arthritis Rheum 38: 969–975

    Article  PubMed  CAS  Google Scholar 

  31. Lohmander LS, Hoerrner LA, Dahlberg L, Roos H, Bjornsson S, Lark MW (1993) Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee fluid after injury. J Rheum 20: 1362–1368

    PubMed  CAS  Google Scholar 

  32. Manicourt DH, Fujimoto N, Obata K, Thonar EJ (1994) Serum levels of collagenase, stromelysin-1 and TIMP-1. Age-and sex-related differences in normal subjects and relationship to the extent of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis. Arthritis Rheum 37: 1774–1783

    Article  PubMed  CAS  Google Scholar 

  33. Sasaki S, Iwata H, Ishiguro N, Obata K, Miura T (1994) Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthritis and osteoarthritis. Clin Rheum 13: 228–233

    CAS  Google Scholar 

  34. Hill PA, Murphy G, Docherty AJP, Hembry RM, Millican TA, Reynolds JJ, Meikle MC (1994) The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts. J Cell Sci 107: 3055–3064

    PubMed  CAS  Google Scholar 

  35. Bord S, Horner A, Hembry RM, Reynolds JJ, Compston JE (1997) Distribution of matrix metalloproteinases and their inhibitor TIMP-1, in developing human osteophyt-ic bone. J Anat 191: 39–48

    Article  PubMed  CAS  Google Scholar 

  36. Hill PA, Docherty AJP, Bottomley KMK, O’Connell JP, Morphy JR, Reynolds JJ, Meik-le MC (1995) Inhibition of bone resorption in vitro by selective inhibitors of gelatinase and collagenase. Biochem J 308: 167–175

    PubMed  CAS  Google Scholar 

  37. Dempster DW (1997) Exploiting and bypassing the bone remodeling cycle to optimize the treatment of osteoporosis. J Bone & Miner Res 12: 1152–1154

    Article  CAS  Google Scholar 

  38. Edwards JC, Wilkinson LS, Soothil P, Hembry RM, Murphy G, Reynolds JJ (1996) Matrix metalloproteinases in the formation of human synovial joint cavities. J Anat 188: 355–360

    PubMed  CAS  Google Scholar 

  39. Stoop R, VanMeurs JBJ, Singer II, Bayne EK, Poole AR, Billinghurst RC, Buma P, Van-Lent PL, VanderKraan PM, VandenBerg WB (1998) The collagenase cleavage site in type II collagen colocalizes with the MMP-generated aggrecan neo-epitope VDIPEN in murine antigen induced arthritis. Trans Orthop Res Soc 23: 851

    Google Scholar 

  40. Muidgett JS, Hutchinson NI, Chartrain NA, Christen AJ, McDonnell J, Singer II, Bayne EK, Flanagan J, Kawka D, Shen CF et al (1998) Susceptibility of stromelysin-1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 41: 110–121

    Article  Google Scholar 

  41. Singer II, Scott S, Kawka DW, Bayne EK, Weidner JR, Williams HR, Mumford RA, Lark MW, McDonnell J, Christen AJ et al (1997) Aggrecanase and metalloproteinase-specific aggrecan neo-epitopes are induced in the articular cartilage of mice with collagen II-induced arthritis. Osteoarthritis Cartilage 5: 407–418

    Article  PubMed  CAS  Google Scholar 

  42. Roos HR, Dahlberg L, Hoerrner LA, Lark MW, Thonar EJMA, Shinmei M, Lindqvist U, Lohmander LS (1995) Markers of cartilage matrix metabolism in human joint fluid and serum: the effect of exercise. Osteoarthritis Cartilage 3: 7–14

    Article  PubMed  CAS  Google Scholar 

  43. Lark MW, Bayne EK, Flanagan J, Harper CF, Hoerrner LA, Hutchinson NI, Singer II, Donatelli SA, Weidner JR, Williams HR et al (1997) Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic and rheumatoid joints. J Clin Invest 100: 93–106

    Article  PubMed  CAS  Google Scholar 

  44. Lark MW, Williams H, Hoerrner LA, Weidner J, Ayala JM, Harper CF, Christen A, Olszewski J, Konteatis Z, Webber R, Mumford RA (1995) Quantification of a matrix metalloproteinase-generated aggrecan Gl fragment using a monospecific anti-peptide serum. Biochem J 307: 245–252

    PubMed  CAS  Google Scholar 

  45. VanMeurs JBJ, vanLent PLEM, Holthuysen AEM, Stoop R, Singer II, Bayne EK, Visco D, Mudgett JS, VandenBerg WB (1998) Expression of the MMP-induced neoepitope FVDIPEN is linked to severe cartilage damage: an essential role for stromelysin in antigen induced arthritis. Trans Orthop Res Soc 23: 856

    Google Scholar 

  46. Bonassar LJ, Frank EH, Murray JC, Paguio CG, Moore VL, Lark MW, Sandy JD, Wu JJ, Eyre DR, Grodzinsky AJ (1995) Changes in cartilage composition and physical properties due to stromelysin degradation. Arthritis Rheum 38: 173–183

    Article  PubMed  CAS  Google Scholar 

  47. Bonassar LJ, Stinn JL, Paguio CG, Frank EH, Moore VL, Lark MW, Grodzinsky AJ (1996) Activation and inhibition of endogenous matrix metalloproteinases in articular cartilage: Effects on composition and biophysical properties. Arch Biochem Biophys 333:359–367

    Article  PubMed  CAS  Google Scholar 

  48. Hughes CE, Caterson B, Fosang AJ, Roughley PJ, Mort JS (1995) Monoclonal antibodies that specifically recognize neoepitope sequences generated by aggrecanase and matrix metalloproteinase cleavage of aggrecan: application to catabolism in situ and in vitro. Biochem J 305: 799–804

    PubMed  CAS  Google Scholar 

  49. Fosang AJ, Last K, Gardiner P, Jackson DC, Brown L (1995) Development of a cleavage site specific monoclonal antibody for detecting metalloproteinase-derived aggrecan fragments: detection of fragments in human synovial fluids. Biochem / 310: 337–343

    CAS  Google Scholar 

  50. Lark MW, Gordy JT, Weidner JR, Ayala J, Kimura JH, Williams HR, Mumford RA, Flannery CR, Carlson SS, Iwata M, Sandy JD (1995) Cell mediated catabolism of aggrecan. Evidence that cleavage at the “aggrecanase” site (Glu373-Ala374) is a primary event in proteolysis of the interglobular domain. J Biol Chem 270: 2550–2556

    Article  PubMed  CAS  Google Scholar 

  51. Hollander AP, Pidoux I, Reiner C, Rorabeck C, Bourne R, Poole AR (1995) Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes and extends into the cartilage with progressive degeneration. J Clin Invest 96: 2859–2869

    Article  PubMed  CAS  Google Scholar 

  52. Sandy JD, Neame PJ, Boynton RE, Flannery CR (1991) Catabolism of aggrecan in cartilage expiants. Identification of a major cleavage site within the interglobular domain. J Biol Chem 266: 8683–8695

    PubMed  CAS  Google Scholar 

  53. Loulakis P, Shrikande A, Davis G, Maniglia CA (1992) N-terminal sequence of proteoglycan fragments isolated from medium of interleukin-1-treated articular cartilage cultures. Biochem J 284: 589–593

    PubMed  CAS  Google Scholar 

  54. Bayliss MT, Holms MWA, Muir H (1989) Age-related changes in the stoichiometry of binding region, link protein and hyaluronic acid in human cartilage. Trans Orthop Res Soc 14: 32

    Google Scholar 

  55. Lohmander LS, Neame P, Sandy JD (1993) The structure of aggrecan fragments in human synovial fluid: Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury and osteoarthritis. Arthritis Rheum 36: 1214–1222

    Article  PubMed  CAS  Google Scholar 

  56. Sandy JD, Flannery CR, Neame PJ, Lohmander LS (1992) The structure of aggrecan fragments in human synovial fluid: Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the glu373-ala374 bond of the interglobular domain. J Clin Invest 89: 1512–1516

    Article  PubMed  CAS  Google Scholar 

  57. Hunziker EB (1992) Articular cartilage structure in humans and experimental animals. In: KE Kuettner, R Schleyerbach, JG Peyron, VC Hascall (eds): Articular cartilage and osteoarthritis. Raven Press, New York, 183–199

    Google Scholar 

  58. Billinghurst RC, Dahlberg L, Ionescu M, Reiner A, Bourne R, Rorabeck C, Mitchell P, Hambor J, Diekmann O, Tschesche H et al (1997) Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest 99: 1534–1545

    Article  PubMed  CAS  Google Scholar 

  59. Shlopov BV, Lie W, Mainardi CL, Cole AA, Chubinskaya S, Hasty KA (1997) Osteoarthritic lesions. Involvement of three different collagenases. Arthritis Rheum 40: 2065–2074

    Article  PubMed  CAS  Google Scholar 

  60. Case JP, Sano H, Lafyatis R, Remmers EF, Kumkumain GK, Wilder RL (1989) Transin/stromelysin expression in the synovium of rats with experimental erosive arthritis. In situ localization and kinetics of the transformation-associated metalloproteinase in euthymic and athymic Lewis rats. J Clin Invest 84: 1731–1740

    Article  PubMed  CAS  Google Scholar 

  61. Hasty KA, Reife RA, Kanh AH, Stuart JM (1990) The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. Arthritis Rheum 34: 1560–1570

    Google Scholar 

  62. Singer II, Kawka DW, Bayne EK, Donatelli SA, Weidner JR, Williams HR, Ayala JM, Mumford RA, Lark MW, Giant TT, Nabozny GH, David CS (1995) VDIPEN, a metal-loproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis. J Clin Invest 9: 2178–2186

    Article  Google Scholar 

  63. Kammermann JR, Kincaid SA, Rumph PF, Baird DK, Visco DM (1996) Tumor necrosis factor-alpha (TNF-alpha) in canine osteoarthritis: Immunolocalization of TNF-alpha, stromelysin and TNF receptors in canine osteoarthritic cartilage. Osteoarthritis Cartilage 4: 23–34

    Article  PubMed  CAS  Google Scholar 

  64. Pelletier JP, Faure MP, DiBattista JA, Wilhelm S, Visco D, Martel-Pelletier J (1993) Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. Am J Path 142: 95–105

    PubMed  CAS  Google Scholar 

  65. Mehraban F, Kuo S-Y, Riera H, Chang C, Moskowitz RW (1994) Prostromelysin and procollagenase genes are differentially up-regulated in chondrocytes from the knees of rabbits with experimental osteoarthritis. Arthritis Rheum 37: 1189–1197

    Article  PubMed  CAS  Google Scholar 

  66. Lark MW, MacNaul KA, Donatelli S, McDonnell J, Hoerrner LA, Stevens KA, Saphos CA, Bayne EK, Hutchinson NI, Moore VL (1994) Induction of increased levels of proteoglycan fragments in synovial fluid (SF) and increased levels of stromelysin in cartilage, synovium and SF by intraarticular injection of canine monocyte conditioned medium. J Rheum 21: 1716–1724

    PubMed  CAS  Google Scholar 

  67. Bayne EK, MacNaul KL, Donatelli S, Christen A, Griffin P, Hoerrner LA, Calaycay J, Ayala J, Chapman K, Hagmann W et al (1995) Detection of stromelysin-generated aggrecan neo-epitope within rabbit articular cartilage. Arthritis Rheum 38: 1400–1409

    Article  PubMed  CAS  Google Scholar 

  68. Bonassar LJ, Jeffries KA, Frank EH, Moore VL, Lark MW, Bayne EK, McDonnell J, Olszewski J, Hagmann W, Chapman K, Grodzinsky AJ (1995) In vivo effects of stromelysin on the composition and physical properties of rabbit articular cartilage in the presence and absence of a synthetic inhibitor. Arthritis Rheum 39: 1678–1686

    Article  Google Scholar 

  69. Olszewski J, McDonnell J, Stevens K, Visco D, Moore V (1996) A matrix metalloproteinase-generated aggrecan neoepitope as a marker of skeletal maturation and aging in cartilage. Arthritis Rheum 39: 1234–1237

    Article  PubMed  CAS  Google Scholar 

  70. Huebner JL, Kraus VB (1998) Collagenase-3 expression in a guinea pig model of osteoarthritis. Trans Orthop Res Soc 14: 460

    Google Scholar 

  71. Dhanaraj V, Ye QZ, Johnson LL, Hupe DJ, Ortwine DF, Dunbar JB, Rubin JR, Pavlovsky A, Humblet C, Blundell TL (1996) Designing inhibitors of the metalloproteinase superfamily: comparative analysis of representative structures. Drug Des Discov 13: 3–14

    PubMed  CAS  Google Scholar 

  72. Becker JW, Marcy AI, Rokosz LL, Axel MG Burbaum JJ, Fitzgerald PMD, Cameron PM, Esser CK, Hagmann WK, Hermes JD, Springer JP (1995) Stromelysin-1: Threedimensional structure of the inhibited catalytic domain and of the C-truncated proen-zyme. Prot Sci 4: 1966–1976

    Article  CAS  Google Scholar 

  73. Gooley PR, O’Connell JF, Marcy AI, Cuca GC, Salowe SP, Bush BL, Hermes JD, Esser CK, Hagmann WK, Springer JP, Johnson BA (1994) The NMR structure of the inhibited catalytic domain of human stromelysin-1. Nature Struct Biol 1: 111–118

    Article  PubMed  CAS  Google Scholar 

  74. Vincenti MP, Clark IM, Brinkerhoff CE (1994) Using inhibitors of metalloproteinases to treat arthritis. Easier said than done? Arthritis Rheum 37: 1115–1126

    Article  PubMed  CAS  Google Scholar 

  75. Hagmann WK, Lark MW, Becker JW (1996) Inhibition of matrix metalloproteinases. Ann Rep Med Chem 31: 231–240

    Article  CAS  Google Scholar 

  76. Sohoo SP, Caldwell CG, Chapman KT, Durette PL, Esser CK, Polo SA, Sperow KM, Niedzwiecki LM, Izquierdo-Martin M, Chang BC et al (1995) Inhibition of matrix metalloproteinases by N-carboxyalkyl dipeptides: enhanced potency and selectivity with substitutes p1’ homophenylalanines. Bioorg Med & Chem Lett 5: 2441–2446

    Article  Google Scholar 

  77. Chapman KT, Wales J, Sahoo SP, Niedzwiecki LM, Izquierdo-Martin M, Chang BC, Harrison RK, Stein RL, MacCoss M, Hagmann WK (1996) Inhibition of matrix metalloproteinases by PI substituted N-carboxyalkyl dipeptides. Bioorg & Med Chem Lett 6: 329–332

    Article  CAS  Google Scholar 

  78. Esser CK, Bugianesi RL, Caldwell CG, Chapman KT, Durrette PL, Girotra NN, Kopka IE, Lanza TJ, Levorse DA, MacCoss M et al (1997) Inhibition of stromelysin-1 (MMP-3) by Pl’biphenylylethyl carboxyalkyl dipeptides. J Med Chem 40: 1026–1040

    Article  PubMed  CAS  Google Scholar 

  79. Conway JG, Wakefield JA, Brown RH, Marron BE, Sekut L, Stimpson SA, McElroy A, Menius JA, Jeffreys JJ, Clark RL et al (1995) Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor. J Exp Med 182:449–457

    Article  PubMed  CAS  Google Scholar 

  80. Lewis EJ, Bishop J, Bottomley KM, Bradshaw D, Brewster M, Broadhurst MJ, Brown PA, Budd JM, Elliott L, Greeham AK et al (1997) Ro 32-3555, an orally active collagenase inhibitor prevents cartilage breakdown in vitro and in vivo. Br J Pharmacol 121: 540–546

    Article  PubMed  CAS  Google Scholar 

  81. O’Byrne EM, Parker DT, Roberts ED, Goldberg RL, MacPherson LJ, Blancuzzi V, Wilson D, Singh HN, Ludweig R, Ganu VS (1995) Oral administration of a matrix metalloproteinase inhibitor CGS 27023A, protects the cartilage proteoglycan matrix in a partial meniscectomy model of osteoarthritis in rabbits. Inflamm Res 44: S117–S118

    Article  CAS  Google Scholar 

  82. Brandt KD (1995) Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis. J Rheumatol (Suppl 43) 22: 149–151

    Google Scholar 

  83. Cole AA, Chubinskaya S, Luchene LJ, Chlebek K, Orth, MW, Greenwald RA, Kuettner KE, Schmid TM (1994) Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation. Arthritis Rheum 12: 1727–1734

    Article  Google Scholar 

  84. Greenwald RA, Golub LM, Lavietes V, Ramamurthy NS, Gruber H, Laskin RS, McNa-mara TF (1987) Tetracyclines inhibit human synovial collagenase in vivo and in vitro. J Rheumat} 14: 28–32

    CAS  Google Scholar 

  85. Yu LP, Smith, Jr. GN, Brandt KD, Myers SL, O’Connor BL, Brandt DA (1992) Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycy-cline. Arthritis Rheum 35(10) 1150–1159

    Article  PubMed  Google Scholar 

  86. Nethery A, Giles I, Jenkins K, Jackson C, Brooks P, Burkhardt D, Ghosh P, Whitlock J, O’Grady RL, Welgus HG, Schrieber L (1992) The chondroprotective drugs, Arteparon and sodium pentosan phosphate, increase collagenase activity and inhibit stromelysin activity in vitro. Biochem Pharmacol 44: 1549–1553

    Article  PubMed  CAS  Google Scholar 

  87. Halverson PB, Cheung HS, Struve J, McCarty DJ (1987) Suppression of active collagenase from calcified lapine synovium by arteparon. / Rheumat 14: 1013–1017

    CAS  Google Scholar 

  88. Fernandes JC, Martel-Pelletier J, Otterness IG, Lopez-Anaya A, Mineau F, Tardif G, Pelletier JP (1995) Effects of Tenidap on canine experimental osteoarthritis. I. Morphologic and metalloprotease analysis. Arthritis Rheum 38: 1290–1303

    Article  PubMed  CAS  Google Scholar 

  89. Nita I, Ghivizzani SC, Galea-Lauri J, Bandara G, Georgescu HI, Robbins PD, Evans CH (1996) Direct gene delivery to synovium. An evaluation of potential vectors in vitro and in vivo. Arthritis Rheum 39: 820–828

    Article  CAS  Google Scholar 

  90. Ikeda T, Kubo T, Kobayashi K, Arai Y, Takahashi K, Nakanishi T, Takigawa M, Iman-ishi J, Hirasawa Y (1997) Adenovirus vector-mediated gene transfer to joints in guinea pig. Trans Orthop Res Soc 22: 430

    Google Scholar 

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Authors and Affiliations

  1. Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, UW2109, 709 Swedeland Road, King of Prussia, PA, 19333, USA

    Michael W. Lark

  2. lmmunology and Inflammation Research, Merck & Co. Inc, PO Box 2000, Rahway, NJ, 07065, USA

    Ellen K. Bayne

  3. Department of Orthopaedics, University Hospital in Lund, S-22185, Lund, Sweden

    L. Stefan Lohmander

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  1. Roche Discovery Welwyn, Roche Products Ltd., 40 Broadwater Road, Welwyn Garden City, GB-Herfordshire, AL7 3AY, UK

    Kevin M. K. Bottomley , David Bradshaw  & John S. Nixon ,  & 

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© 1999 Springer Basel AG

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Lark, M.W., Bayne, E.K., Lohmander, L.S. (1999). Role of stromelysin-1 in cartilage metabolism. In: Bottomley, K.M.K., Bradshaw, D., Nixon, J.S. (eds) Metalloproteinases as Targets for Anti-Inflammatory Drugs. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8666-6_3

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  • DOI: https://doi.org/10.1007/978-3-0348-8666-6_3

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9724-2

  • Online ISBN: 978-3-0348-8666-6

  • eBook Packages: Springer Book Archive

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