RESEARCH PROGRESS OF A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIF 4 AND 5 IN OSTEOARTHRITIS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

JI Quanbo , ZHANG Qiang , WANG Yan.

Department of Orthopedics, the General Hospital of Chinese PLA, Beijing, 100853, P.R.China. Corresponding author: WANG Yan, E-mail: yanwang301@yahoo.com;

Corresponding author：

Keywords：

A disintegrin and metalloproteinase with thrombospondin motif; Aggrecanase; Osteoarthritis

DOI：

10.7507/1002-1892.20130236

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Objective To review the progress of a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS-4) and ADAMTS-5 in osteoarthritis. Methods Recent literature about the ADAMTS-4 and -5 in osteoarthritis was analyzed; the structure, function, inhibitors of the ADAMTS-4 and -5, and the relationship between the proteases and osteoarthritis were analyzed and summarized. Results ADAMTS-4 and -5 can reduce chondrocyte and extracellular matrix by degrading aggrecan and cartilage oligomeric matrix protein, which induced the pathogenesis of osteoarthritis. Conclusion ADAMTS-4 and -5 have been demonstrated to play important roles in osteoarthritis. It can better guide treatment and prevention of osteoarthritis to further study related mechanism of ADAMTS-4 and -5, and to promote the establishment of a clinical drug targets.

Citation： JI Quanbo,ZHANG Qiang,WANG Yan.. RESEARCH PROGRESS OF A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIF 4 AND 5 IN OSTEOARTHRITIS. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(9): 1080-1084. doi: 10.7507/1002-1892.20130236 Copy

1.	Matel-Pelletier J, Boileau C, Pelletier JP, et al. Cartilage innormal and osteoarthritis conditions. Best Pract Res Clin Rheumatol, 2008, 22(2): 351-384．.
2.	Verma P, Dalal K. ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. J Cell Biochem, 2011, 112(12): 3507-3514.
3.	Song RH, Tortorella MD, Malfait AM, et al. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum, 2007, 56(2): 575-585．.
4.	Bondeson J, Wainwright S, Hughes C, et al. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clin Exp Rheumatol, 2008, 26(1): 139-145.
5.	Kuno K, Kanada N, Nakashima E, et al. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem, 1997, 272(1): 556-562.
6.	Porter S, Clark IM, Kevorkian L, et al. The ADAMTS metalloproteinases. J Biochem, 2005, 386(Pt 1): 15-27.
7.	Gantus MA, Nasciutti LE, Cruz CM, et al. Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve. Brain Res, 2006, 1122(1): 36-46.
8.	Tortorella M, Pratta M, Liu RQ, et al. The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. J Biol Chem, 2000, 275(33): 25791-25797.
9.	Fosang AJ, Rogerson FM, East CJ, et al. ADAMTS-5: the story so far．Eur Cell Mater, 2008, 15: 11-26.
10.	Tortorella MD, Arner EC, Hills R, et al. ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms. Arch Biochem Biophys, 2005, 444(1): 34-44.
11.	Thirunavukkarasu K, Pei Y, Moore TL, et al. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines. Biochem Biophys Res Commun, 2006, 345(1): 197-204.
12.	Saito T, Nishida K, Ozaki T, et al. Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes. Osteoarthritis Cartilage, 2013, 21(1): 165-174.
13.	Bateman JF, Rowley L, Belluoccio D, et al. Transcriptomics of wild type mice and mice lacking ADAMTS-5 activity identifies genes involved in osteoarthritis initiation and cartilage destruction. Arthritis Rheum, 2013, 65(6): 1547-1560.
14.	Yamamoto K, Troeberg L, Scilabra SD, et al. LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage. FASEB J, 2013, 27(2): 511-521.
15.	Sylvester J, Ahmad R, Zafarullah M. Role of Sp1 transcription factor in Interleukin-1-induced ADAMTS-4 (aggrecanase-1) gene expression in human articular chondrocytes. Rheumatol Int, 2013, 33(2): 517-522.
16.	Mimata Y, Kamataki A, Oikawa S, et al. Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Int J Rheum Dis, 2012, 15(1): 36-44.
17.	Hussein MR, Fathi NA, El-Din AM, et al. Alterations of the CD4(+), CD8(+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factor-alpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations. Pathol Oncol Res, 2008, 14(3): 321-328.
18.	Joosten LA, Helsen MM, Saxne T, et al. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol, 1999, 163(9): 5049-5055.
19.	Zwerina J, Redlich K, Polzer K, et al. TNF-induced structural joint damage is mediated by IL-1. Proc Natl Acad Sci U S A, 2007, 104(28): 11742-11747.
20.	Rogerson FM, Chung YM, Deutscher ME, et al. Cytokine-induced increases in ADAMTS-4 messenger RNA expression do not lead to increased aggrecanase activity in ADAMTS-5-deficient mice. Arthritis Rheum, 2010, 62(11): 3365-3373.
21.	Yamanishi Y, Boyle DL, Clark M, et al. Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol, 2002, 168(3): 1405-1412.
22.	Naito S, Shiomi T, Okada A, et al. Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage. Pathol Int, 2007, 57(11): 703-711.
23.	Stanton H, Rogerson FM, East CJ, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature, 2005, 434(7033): 648-652.
24.	Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature, 2007, 434(7033): 644-648.
25.	Majumdar MK, Askew R, Schelling S, et al. Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. Arthritis Rheum, 2007, 56(11): 3670-3674.
26.	Cheung KS, Hashimoto K, Yamada N, et al. Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA demethylation. Rheumatol Int, 2009, 29(5): 525-534.
27.	Little CB, Hughes CE, Curtis CL, et al. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. Matrix Biol, 2002, 21(3): 271-288．.
28.	Karsdal MA, Madsen SH, Christiansen C, et al. Cartilage degradation is fully reversible in the presence of aggrecanase but not matrixmetalloproteinase activity. Arthritis Res Ther, 2008, 10(3): R63.
29.	Guilak F, Alexopoulos LG, Upton ML, et al. The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Ann N Y Acad Sci, 2006, 1068: 498-512.
30.	Kashiwagi M, Tortorella M, Nagase H, et al. TIMP-3 is a potent inhibitor of aggrecanase 1(ADAMTS-4) and aggrecanase 2 (ADAMTS-5). J Biol Chem, 2001, 276(16): 12501-12504.
31.	Lim NH, Kashiwagi M, Visse R, et al. Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications. Biochem J, 2010, 431(1): 113-122.
32.	Wayne GJ, Deng SJ, Amour A, 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(29): 20991-20998.
33.	Jayasuriya CT, Goldring MB, Terek R, et al. Matrilin-3 induction of IL-1 receptor antagonist is required for up-regulating collagen II and aggrecan and down-regulating ADAMTS-5 gene expression. Arthritis Res Ther, 2012, 14(5): R197.
34.	Groma G, Grskovic I, Schael S, et al. Matrilin-4 is processed by ADAMTS-5 in late Golgi vesicles present in growth plate chondrocytes of defined differentiation state. Matrix Biol, 2011, 30(4): 275-280.
35.	Tortorella MD, Arner EC, Hills R, 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(17): 17554-17561.
36.	Enghild JJ, Salvesen G, Brew K, et al. Interaction of human rheumatoid synovial collagenase (matrix metalloproteinase 1) and stromelysin (matrix metalloproteinase 3) with human alpha 2-macroglobulin and chicken ovostatin. Binding kinetics and identification of matrix metalloproteinase cleavage sites. J Biol Chem, 1989, 264(15): 8779-8785.
37.	Moncada-Pazos A, Obaya AJ, Viloria CG, et al. The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities. J Mol Med (Berl), 2011, 89(6): 611-619.
38.	Chia SL, Sawaji Y, Burleigh A, et al. Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheum, 2009, 60(7): 2019-2027.
39.	Krarnemva IA, Kawaguehi N, Fessler LI, et al. Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinase. Development, 2000, 127(24): 5475-5485.
40.	Gabay O, Sanchez C, Salvat C, et al. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties. Osteoarthritis Cartilage, 2010, 18(1): 106-116.
41.	Cudic M, Burstein GD, Fields GB, et al. Analysis of flavonoid-based pharmacophores that inhibit aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases through the use of topologically constrained peptide substrates. Chem Biol Drug Des, 2009, 74(5): 473-482.
42.	Fosang AJ, Last K, Stanton H, et al. Neoepitope antibodies against MMP-cleaved and aggrecanase-cleaved aggrecan. Methods Mol Biol, 2010, 622: 312-347.
43.	Lakey RL, Cawston TE. Sulfasalazine blocks the release of proteoglycan and collagen from cytokine stimulated cartilage and down-regulates metalloproteinases. Rheumatology (Oxford), 2009, 48(10): 1208-1212.

1. Matel-Pelletier J, Boileau C, Pelletier JP, et al. Cartilage innormal and osteoarthritis conditions. Best Pract Res Clin Rheumatol, 2008, 22(2): 351-384．.
2. Verma P, Dalal K. ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. J Cell Biochem, 2011, 112(12): 3507-3514.
3. Song RH, Tortorella MD, Malfait AM, et al. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum, 2007, 56(2): 575-585．.
4. Bondeson J, Wainwright S, Hughes C, et al. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clin Exp Rheumatol, 2008, 26(1): 139-145.
5. Kuno K, Kanada N, Nakashima E, et al. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem, 1997, 272(1): 556-562.
6. Porter S, Clark IM, Kevorkian L, et al. The ADAMTS metalloproteinases. J Biochem, 2005, 386(Pt 1): 15-27.
7. Gantus MA, Nasciutti LE, Cruz CM, et al. Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve. Brain Res, 2006, 1122(1): 36-46.
8. Tortorella M, Pratta M, Liu RQ, et al. The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. J Biol Chem, 2000, 275(33): 25791-25797.
9. Fosang AJ, Rogerson FM, East CJ, et al. ADAMTS-5: the story so far．Eur Cell Mater, 2008, 15: 11-26.
10. Tortorella MD, Arner EC, Hills R, et al. ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms. Arch Biochem Biophys, 2005, 444(1): 34-44.
11. Thirunavukkarasu K, Pei Y, Moore TL, et al. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines. Biochem Biophys Res Commun, 2006, 345(1): 197-204.
12. Saito T, Nishida K, Ozaki T, et al. Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes. Osteoarthritis Cartilage, 2013, 21(1): 165-174.
13. Bateman JF, Rowley L, Belluoccio D, et al. Transcriptomics of wild type mice and mice lacking ADAMTS-5 activity identifies genes involved in osteoarthritis initiation and cartilage destruction. Arthritis Rheum, 2013, 65(6): 1547-1560.
14. Yamamoto K, Troeberg L, Scilabra SD, et al. LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage. FASEB J, 2013, 27(2): 511-521.
15. Sylvester J, Ahmad R, Zafarullah M. Role of Sp1 transcription factor in Interleukin-1-induced ADAMTS-4 (aggrecanase-1) gene expression in human articular chondrocytes. Rheumatol Int, 2013, 33(2): 517-522.
16. Mimata Y, Kamataki A, Oikawa S, et al. Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Int J Rheum Dis, 2012, 15(1): 36-44.
17. Hussein MR, Fathi NA, El-Din AM, et al. Alterations of the CD4(+), CD8(+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factor-alpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations. Pathol Oncol Res, 2008, 14(3): 321-328.
18. Joosten LA, Helsen MM, Saxne T, et al. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol, 1999, 163(9): 5049-5055.
19. Zwerina J, Redlich K, Polzer K, et al. TNF-induced structural joint damage is mediated by IL-1. Proc Natl Acad Sci U S A, 2007, 104(28): 11742-11747.
20. Rogerson FM, Chung YM, Deutscher ME, et al. Cytokine-induced increases in ADAMTS-4 messenger RNA expression do not lead to increased aggrecanase activity in ADAMTS-5-deficient mice. Arthritis Rheum, 2010, 62(11): 3365-3373.
21. Yamanishi Y, Boyle DL, Clark M, et al. Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol, 2002, 168(3): 1405-1412.
22. Naito S, Shiomi T, Okada A, et al. Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage. Pathol Int, 2007, 57(11): 703-711.
23. Stanton H, Rogerson FM, East CJ, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature, 2005, 434(7033): 648-652.
24. Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature, 2007, 434(7033): 644-648.
25. Majumdar MK, Askew R, Schelling S, et al. Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. Arthritis Rheum, 2007, 56(11): 3670-3674.
26. Cheung KS, Hashimoto K, Yamada N, et al. Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA demethylation. Rheumatol Int, 2009, 29(5): 525-534.
27. Little CB, Hughes CE, Curtis CL, et al. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. Matrix Biol, 2002, 21(3): 271-288．.
28. Karsdal MA, Madsen SH, Christiansen C, et al. Cartilage degradation is fully reversible in the presence of aggrecanase but not matrixmetalloproteinase activity. Arthritis Res Ther, 2008, 10(3): R63.
29. Guilak F, Alexopoulos LG, Upton ML, et al. The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Ann N Y Acad Sci, 2006, 1068: 498-512.
30. Kashiwagi M, Tortorella M, Nagase H, et al. TIMP-3 is a potent inhibitor of aggrecanase 1(ADAMTS-4) and aggrecanase 2 (ADAMTS-5). J Biol Chem, 2001, 276(16): 12501-12504.
31. Lim NH, Kashiwagi M, Visse R, et al. Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications. Biochem J, 2010, 431(1): 113-122.
32. Wayne GJ, Deng SJ, Amour A, 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(29): 20991-20998.
33. Jayasuriya CT, Goldring MB, Terek R, et al. Matrilin-3 induction of IL-1 receptor antagonist is required for up-regulating collagen II and aggrecan and down-regulating ADAMTS-5 gene expression. Arthritis Res Ther, 2012, 14(5): R197.
34. Groma G, Grskovic I, Schael S, et al. Matrilin-4 is processed by ADAMTS-5 in late Golgi vesicles present in growth plate chondrocytes of defined differentiation state. Matrix Biol, 2011, 30(4): 275-280.
35. Tortorella MD, Arner EC, Hills R, 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(17): 17554-17561.
36. Enghild JJ, Salvesen G, Brew K, et al. Interaction of human rheumatoid synovial collagenase (matrix metalloproteinase 1) and stromelysin (matrix metalloproteinase 3) with human alpha 2-macroglobulin and chicken ovostatin. Binding kinetics and identification of matrix metalloproteinase cleavage sites. J Biol Chem, 1989, 264(15): 8779-8785.
37. Moncada-Pazos A, Obaya AJ, Viloria CG, et al. The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities. J Mol Med (Berl), 2011, 89(6): 611-619.
38. Chia SL, Sawaji Y, Burleigh A, et al. Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheum, 2009, 60(7): 2019-2027.
39. Krarnemva IA, Kawaguehi N, Fessler LI, et al. Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinase. Development, 2000, 127(24): 5475-5485.
40. Gabay O, Sanchez C, Salvat C, et al. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties. Osteoarthritis Cartilage, 2010, 18(1): 106-116.
41. Cudic M, Burstein GD, Fields GB, et al. Analysis of flavonoid-based pharmacophores that inhibit aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases through the use of topologically constrained peptide substrates. Chem Biol Drug Des, 2009, 74(5): 473-482.
42. Fosang AJ, Last K, Stanton H, et al. Neoepitope antibodies against MMP-cleaved and aggrecanase-cleaved aggrecan. Methods Mol Biol, 2010, 622: 312-347.
43. Lakey RL, Cawston TE. Sulfasalazine blocks the release of proteoglycan and collagen from cytokine stimulated cartilage and down-regulates metalloproteinases. Rheumatology (Oxford), 2009, 48(10): 1208-1212.

Chinese Journal of Reparative and Reconstructive Surgery

RESEARCH PROGRESS OF A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIF 4 AND 5 IN OSTEOARTHRITIS

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