Abstract
Osteoarthritis (OA) is a disease characterized by a degeneration of articular cartilage. Although the etiology of OA is not yet known and is likely multifactorial, this disease process involves a disturbance in the normal balance of degradation and repair in articular cartilage (1). The breakdown of the cartilage matrix leads to the development of fibrillation, fissures, the appearance of gross ulcerations, and the disappearance of the full thickness surface of the joint. This is accompanied by hypertrophic bone changes with osteophyte formation and subchondral plate thickening. The cartilage matrix breakdown products released into the synovial fluid are phagocytosed by the synovial membrane. Consequently, the membrane becomes hypertrophic and hyperplastic, and an inflammatory reaction is often observed. Although the remodeling of subchondral bone is associated with OA pathology, it is still under debate whether this tissue change initiates or is involved in the progression of cartilage loss.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Pelletier, J. P., Martel-Pelletier, J., and Howell, D. S. (1997) Etiopathogenesis of osteoarthritis, in Arthritis and Allied Conditions. A Textbook ofRheumatology (Koopman, W. J., ed.), Williams & Wilkins, Baltimore, pp. 1969–1984.
Tortorella, M. D., Burn, T. C., Pratta, M. A., Abbaszade, I., Hollis, J. M., Liu, R., et. al. (1999) Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science 284, 1664–1666.
Birkedal-Hansen, H., Moore, W. G., Bodden, M. K., Windsor, L. J., Birkedal-Hansen, B., DeCarlo, A., et al. (1993) Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4, 197–250.
Massova, I., Kotra, L. P., Fridman, R., and Mobashery, S. (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J. 12, 1075–1095.
Pei, D. (1999) Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP. J. Biol. Chem. 274, 8925–8932.
Velasco, G., Cal, S., Merlos-Suarez, A., Ferrando, A. A., Alvarez, S., et al. (2000) Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors. Cancer Res. 60, 877–882.
Martel-Pelletier, J. and Pelletier, J. P. (1996) Wanted—the collagenase responsible for the destruction of the collagen network in human cartilage. Br. J. Rheumatol. 35, 818–820.
Fernandes, J. C., Martel-Pelletier, J., Lascau-Coman, V., Moldovan, F., Jovanovic, D., Raynauld, J. P., et al. (1998) Collagenase-1 and collagenase-3 synthesis in early experimental osteoarthritic canine cartilage An immunohistochemical study. J. Rheumatol. 8, 1585–1594.
Laiho, M. and Keski-Oja, J. (1989) Growth factors in the regulation of pericellular proteolysis: a review. Cancer Res. 49, 2533–2553.
Vincenti, M. P., White, L. A., Schroen, D. J., Benbow, U., and Brinckerhoff, C. E. (1996) Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability. Crit. Rev. Eukaryocyte Gene Express 6, 391–411.
Benbow, U. and Brinckerhoff, C. E. (1997) The AP-1 site and MMP gene regulation: what is all the fuss about? Matrix Biol. 15, 519–526.
Mauviel, A., Chung, K. Y., Agarwal, A., Tamai, K., and Uitto, J. (1996) Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes. J Biol Chem 271, 10,917–10,923.
Tardif, G., Pelletier, J. P., Dupuis, M., Geng, C. S., Cloutier, J. M., and Martel-Pelletier, J. (1999) Collagenase-3 production by human OA chondrocytes in response to growth factors and cytokines is a function of the physiological state of the cells: TGF-β preferentially upregulates collagenase-3 production. Arthritis Rheum. 42, 1147–1158.
Nagase, H. (1997) Activation mechanisms of matrix metalloproteinases. Biol. Chem. 378, 151–160.
Gomez, D. E., Alonso, D. F., Yoshiji, H., and Thorgeirsson, U. P. (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur. J. Cell Biol. 74, 111–122.
Beckett, R. and Whittaker, M. (1998) Matrix metalloproteinase inhibitors. Exp. Opin. Ther. Patents 8, 259–282.
Cawston, T. E. (1996) Metalloproteinase inhibitors and the prevention of connective tissue breakdown. Pharmacol. Ther. 70, 163–182.
Wojtowicz-Praga, S. M., Dickson, R. B., and Hawkins, M. J. (1997) Matrix metalloproteinase inhibitors. Invest. New Drugs 15, 61–75.
Gomis-Ruth, F. X., Maskos, K., Betz, M., Bergner, A., Huber, R., et al. (1997) Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature 389, 77–81.
Huang, W., Meng, Q., Suzuki, K., Nagase, H. and Brew, K. (1997) Mutational study of the amino-terminal domain of human tissue inhibitor of metalloproteinases 1 (TIMP-1) locates an inhibitory region for matrix metalloproteinases. J. Biol. Chem. 272, 22,086–22,091.
Levy, D. and Ezrin, A. (1997) Matrix metalloproteinase inhibitor drugs. Emerg. Drugs 2, 205–230.
van den Berg, W. B. (1995) Growth factors in experimental osteoarthritis: transforming growth factor beta pathogenic? J. Rheumatol. 43(Suppl.), 143–145.
Saha, N., Moldovan, F., Tardif, G., Pelletier, J. P., Cloutier, J. M., Martel-Pelletier, J. (1999) Interleukin-1 β-converting enzyme/caspase-1 in human osteoarthritic tissues: localization and role in the maturation of IL-1β and IL-18. Arthritis Rheum. 42, 1577–1587.
Caron, J. P., Fernandes, J. C., Martel-Pelletier, J., Tardif, G., Mineau, F., Geng, C., et al. (1996) Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis: suppression of collagenase-1 expression. Arthritis Rheum. 39, 1535–1544.
Evans, C. H., Stefanovic-Racic, M., and Lancaster, J. (1995) Nitric oxide and its role in orthopaedic disease. Clin. Orthop. 312, 275–294.
Pelletier, J. P., Jovanovic, D., Fernandes, J. C., Manning, P. T., Connor, J. R., Currie, M. G., et al. (1998) Reduced progression of experimental osteoarthritis in vivo by selective inhibition of inducible nitric oxide synthase. Arthritis Rheum. 41, 1275–1286.
Evans, C. H. and Robbins, P. D. (1994) Gene therapy for arthritis, in Gene Therapeutics: Methods and Applications of Direct Gene Transfer (Wolff, J. A., ed.), Birkhauser, Boston, pp. 320–343.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Martel-Pelletier, J., Tardif, G., Fernandes, J., Pelletier, JP. (2000). Metalloproteases and Their Modulation as Treatment in Osteoarthritis. In: Tsokos, G.C. (eds) Principles of Molecular Rheumatology. Current Molecular Medicine, vol 1. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-018-6_33
Download citation
DOI: https://doi.org/10.1007/978-1-59259-018-6_33
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-182-0
Online ISBN: 978-1-59259-018-6
eBook Packages: Springer Book Archive