ETÇİLLERDE KARŞILAŞILAN EKLEM HASTALIKLARINDA MATRİKS METALLOPROTEİNAZLARININ ROLÜ VE SAĞALTIM SEÇENEKLERİ

Abstract

Eklem hastalıklarında karşılaşılan kıkırdak ve kemik doku yıkımlanmasından sorumlu başlıca maddeler; kollajen ve proteoglikanı yıkımlayan proteinazlardır. Proteolitik enzimlerin 4 ana sınıfı olan aspartik proteinazlar, sistein proteinazlar, serin proteinazlar ve metalloproteinazlar destek dokunun hem normal hareketinde, hem de patolojik yıkımında iş görürler. Bu proteinazlar, eklem içinde farklı hücreler tarafından hazırlanırlar. Her bir enzim, etkilerini durduran, özel protein benzeri inhibitörler tarafından inhibe edilebilir. Son araştırmalar, matriks metalloproteinazlarının eklem hastalıklarındaki birçok sürece karıştığına işaret etmektedirler. Eklem yangılarında (artritis) kıkırdak ve kemiğin yıkımlanması, eklemi normal bir şekilde işlev görmekten alıkoymaktadır. Birçok olayda, eklem yüzeyinin geniş bir bölümü ile birlikte, bu kısmın altındaki kemik de zarar görmüştür. Geleneksel tedaviler, bu hastalığın altında yatan süreçlere çok az etki ederler ve son zamanlarda, proteinaz inhibitörlerinin kullanımı, yeni bir terapötik yaklaşım olarak önerilmektedir. Proteinaz inhibitörleri, model sistemlerde, hastanın kıkırdak yıkımını önleyebilir ve gelecekteki deneysel çalışmalar, bu maddelerin in vivo etkinliklerini ortaya koyabilecektir.

Keywords

• Matriks metalloproteinazları,Artritis

THE ROLE OF MATRIX METALLOPROTEINASES IN CANINE JOINT DISEASES AND TREATMENT APPROACHES

Abstract

Proteinases that degrade collagen and proteoglycan are mainly responsible for disintegration of cartilage and bone in joint diseases. Four major classes of proteolytic enzymes which aspartic proteinases, cysteine proteinases, serine proteinases and metalloproteinases perform in normal functioning of connective tissue as well as its pathological destruction. These proteinases prepared by different cells within the joint. Each enzyme may be inhibited by specific protein-like inhibitors which block its effect. The recent research indicate that matrix metalloproteinases involved in many processes in joint diseases. In joint inflammation (arthritis), the degradation of cartilage and bone prevented the joint from functioning in a normal way. In many cases, the large portion of articular surface with underneath bone damaged as well. Conventional therapies have little effect on the underlying processes of this diseases and recently, the use of protease inhibitors proposed as a novel therapeutic approach. In model systems, proteinase inhibitors could prevent cartilage damage in patients and future experimental studies may reveal in vivo activities of these substances.

Keywords

• Matrix metalloproteinases,Arthritis

References

1. 1. Arsenis C, Moak SA, Greenwald RA. Tetracyclines inhibit the synthesis and / or activity of cartilage proteinases in vivo and in vitro. Matrix-Suppl., 1992; 1: 314.
2. 2. Benton HP. Effect of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis and prostaglandin release by cultured osteoarthritic canine condrocytes. AJVR, 1997; 58 (3): 286-292.
3. 3. Birkedal-Hansen H, Moore WGI, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA. Matrix metalloproteinases: A review. Critical Reviews in Oral Biology and Medicine, 1993; 4 (2): 197-250.
4. 4. Cawstone TE. Proteinases and inhibitors. British Med. Bull., 1995; 51 (2): 385-401.
5. 5. Fife RS, Sledge GWJr. Effects of doxycycline on in vitro growth, migration and gelatinase activity of breast carcinoma cells. J.Lab.Clin.Med., 1995; 125 (3): 407-411.
6. 6. Fox SM. Use of carprofen for the treatment of pain and inflammation in dogs. JAVMA, 1997; 210 (10): 1493-1498.
7. 7. Gabler WL, Creamer HR. Suppression of human neutrophil functions by tetracyclines. J.Periodon.Res., 1991, 26: 52-58.
8. 8. Gilbertson-Beadling S, Powers EA, Stamp-Cole M. et al. The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism. Cancer Chemother.Pharmacol., 1995; 36: 418-424.

9. 9. Golub LM, Lee HM, Lehrer G, Ramamurthy NS, McNamara TF. Minocycline reduces gingival collagenolytic activity during diabetes: Preliminary observations and a proposed new mechanism of action. J.Periodont.Res., 1983; 18: 516-524.
10. 10. Golub LM, Wolff M, Lee HM. et al. Furher evidence that tetracyclines inhibit collagenase activity in human crevicular fluid and from other mammalian sources. J.Periodont.Res., 1985, 20: 12-23.
11. 11. Golub LM, Ramamurthy NS, McNamara TF. et al. Tetracyclines inhibit connective tissue breakdown: New therapeutic implications for an old family drugs. Crit.Rev.Oral Med.Pathol., 1991, 2: 297-322.
12. 12. Golub LM, Sorsa T, Lee HM. et al. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J.Clin.Periodont., 1995; 22: 100-109.
13. 13. Gomes BC, Golub LM, Ramamurthy NS. Tetracyclines inhibit parathyroid hormone induced bone resorption in organ culture. Experientia, 1985; 40: 1273-1275.
14. 14. Gordon JL, Drummond AH, Galloway, WA. Metalloproteinase inhibitors as therapeutics. Clin.Exp.Rheum., 1993; 11, (Suppl.): S91-S94.
15. 15. Greenwald RA, Goub LN. Tetracyclines in arthritis. J.Rheum., 1993; 20 (11): 1990.
16. 16. Hewitt RE, Corcoran ML, Stetler-Stevenson WG. The activation, expression and function of gelatinase A (MMP-2). Trends in Glycoscience and Glycotechnology, 1996; 8 (39): 23-36.
17. 17. Hirose T, Reife RA, Smith GN, Stevens RM, Mainardi CL, Hasty KA. Characterization of type IV collagenase (gelatinase) in synovial fluid patients with inflammatory arthritis. J.Rheum., 1992; 19: 593-599.
18. 18. Ingman T, Sorsa T, Suomalainen K, et al. Tetracyline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. J.Periodont., 1993; 64 (2): 82-88.
19. 19. Johnston SA. Osteoarthritis: Joint anatomy, physiology and pathobiology. Vet.Clin.North America: Small An. Practice, 1997; 27 (4): 699-723.
20. 20. Johnston SA, Budsberg SC. Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis. Vet.Clin.North America: Small An. Practice, 1997; 27 (4): 841-861.
21. 21. Kaya, S. (1997) Tetrasiklinler. 349-356. Alındı: Kaya, S. ve ark. (Es): Veteriner Uygulamalı Farmakoloji. Cilt: 2, Medisan Yayınevi, Ankara.
22. 22. Lauhio A, Sorsa T, Lindy O, et al. The anticollagenolytic potential of lymecyclin in the long-term treatment of reactive arthritis. Arthritis and Rheum., 1992; 35 (2): 195-198.
23. 23. Martin RR, Warr GA, Couch RB, et al. Effects of tetracycline on leukotaxis. J.Infect.Dis., 1974; 129: 110-116.
24. 24. McKellar QA, Dekatour P, Lees P. Stereospecific pharmacodynamics and pharmacokinetics of carprofen in the dog. J.Vet.Pharma.Therap., 1994; 17: 447-454.
25. 25. McNamara PS, Johnston SA. Slow acting, disease-modifying osteoarthritis agents. Vet.Clin.North America: Small An. Practice, 1997; 27 (4): 863-881.
26. 26. Mathews KA. Nonsteroidal anti-inflammatory analgesics in pain management in dogs and cats. Can.Vet.J., 1996; 37: 539-545.
27. 27. Mathews KA. Therapeutics in practice: Nonsteroidal anti-inflammatory analgesics to manage acute pain in dogs and cats. The Compendium, 1996; small animal 1117-small animal 1123.
28. 28. Matrisian LM. The matrix-degrading metalloproteinases. BioEssays, 1992; 14 (7): 455-463.
29. 29. Nagase H, Barrett AJ, Woesner JF. Nomenclature and glossary of the matrix metalloproteinases. Matrix,Suppl., 1992; 1: 421-424.
30. 30. Nagase H. Matrix metalloproteinases (A mini review). Extracellular Matrix in the Kidney. Contrib. Nephrol., 1994; 107: 85-93.
31. 31. Nagase H, Okada Y. (1997) Proteinases and matrix degradation. In: Textbook of Rheumatology, fifth ed. Kelley, W.N., Harris, E.D., Ruddy, S. and Sledge, C.B. W.B. Saunders Company. 323-341.
32. 32. Nip LH, Uitto VJ, Golub LM. Inhibition of epithelial cell matrix metalloproteinases by tetracyclines. J. Periodont. Res., 1993; 28: 379-385.
33. 33. Sağlam M, Aştı RN, Özer A. (1997) Bağ ve kıkırdak doku. 135-186. Alındı: Genel Histoloji. Düzeltilmiş beşinci baskı. Yorum matbaacılık sanayii, Ankara.
34. 34. Stocker W, Bode W. Structural features of superfamily of zinc-endopeptidases: The metzincs. Current Opinion in Structural Biology, 1995; 5: 383-390.
35. 35. Thong YH, Ferrate A. Effect of tetracycline treatment on immunological response in mice. Clin. Exp. Immunol., 1980; 39: 728-732.
36. 36. Vallee B, Auld D. Zinc coordination, function and structure of zinc enzymes and other proteins. Biochem., 1990; 29: 5647-5659.
37. 37. Vasseur PB, Johnson AL, Budsberg SC, et al. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs. JAVMA, 1995; 206 (6): 807-811.
38. 38. Van Wart HE, Birkedal-Hansen H. The cyctein switch: A principle of regulation of metalloproteinase gene family. Proc. Natl. Acad. Sci. USA, 1990; 87: 5578-5582.
39. 39. Yu LPJr, Smith GN, Hasty KA, et al. Doxycycline inhibits type IV collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase. J. Rheum., 1991; 18: 1450-1452.