Aggrecanase: A Target for the Design of Inhibitors of Cartilage Degradation
- 1 June 1999
- journal article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 878 (1), 92-107
- https://doi.org/10.1111/j.1749-6632.1999.tb07676.x
Abstract
In arthritic diseases there is a gradual erosion of cartilage that leads to a loss of joint function. Aggrecan, which provides cartilage with its properties of compressibility and elasticity, is the first matrix component to undergo measurable loss in arthritis. This loss of aggrecan appears to be due to an increased rate of degradation, that can be attributed to proteolytic cleavage of the core protein within the interglobular domain (IGD). Two major sites of cleavage have been identified within the IGD. One, between the amino acids Asn341-Phe342, where the matrix metalloproteinases (MMPs) have been shown to clip; and the other, between Glu373-Ala374, which is attributed to a novel protease, "aggrecanase." We have generated aggrecanase in conditioned media from IL-1-stimulated bovine nasal cartilage and have used an enzymatic assay to evaluate this proteinase activity. In these studies we follow the generation of aggrecanase and MMPs in response to IL-1 in this system and examine the contribution of these enzymes in aggrecan degredation. Our data suggest that aggrecanase is a key enzyme in cartilage aggrecan degradation that represents a novel target for cartilage protection therapy in arthritis.Keywords
This publication has 21 references indexed in Scilit:
- Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetiiCellular Microbiology, 2007
- Generation and Characterization of AggrecanaseJournal of Biological Chemistry, 1999
- Cytokine-induced cartilage proteoglycan degradation is mediated by aggrecanaseOsteoarthritis and Cartilage, 1998
- Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13)FEBS Letters, 1996
- An Assay for Matrix Metalloproteinases and Other Proteases Acting on Proteoglycans, Casein, or GelatinAnalytical Biochemistry, 1993
- Mechanism of catabolism of aggrecan by articular cartilageArchives of Biochemistry and Biophysics, 1992
- Modulation of interleukin‐1–induced alterations in cartilage proteoglycan metabolism by activation of protein kinase CArthritis & Rheumatism, 1991
- Factors involved in the regulation of proteoglycan metabolism in articular cartilageArthritis & Rheumatism, 1989
- A Direct Spectrophotometric Microassay for Sulfated Glycosaminoglycans in Cartilage CulturesConnective Tissue Research, 1982
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970