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J Biol Chem, Vol. 273, Issue 28, 17451-17458, July 10, 1998

Characterization of Aggrecan Retained and Lost from the Extracellular Matrix of Articular Cartilage
INVOLVEMENT OF CARBOXYL-TERMINAL PROCESSING IN THE CATABOLISM OF AGGRECAN

Mirna Z. Ilic, H. Clem Robinson^§, and Christopher J. Handley

From the  School of Human Biosciences, La Trobe University, Bundoora 3083, Victoria, Australia and the ^§ Department of Biochemistry and Molecular Biology, Monash University, Clayton 3168, Victoria, Australia

The catabolism of aggrecan in bovine articular cartilage explants is characterized by the release into the culture medium of high molecular weight aggrecan fragments, generated by the proteolytic cleavage of the core protein between residues Glu³⁷³ and Ala³⁷⁴ within the interglobular domain. In this study, the position of the carboxyl-terminus of these aggrecan fragments, as well as a major proteolytically shortened aggrecan core protein present in cartilage matrix, have been deduced by characterizing the peptides generated by the reaction of aggrecan core protein peptides with cyanogen bromide. It was shown that two out of three such peptide fragments having an amino terminus starting at Ala³⁷⁴ have their carboxyl terminus located within the chondroitin sulfate 1 domain. The third and largest aggrecan core protein peptide, with an amino terminus starting at Ala³⁷⁴, has a carboxyl terminus in a region of core protein between the chondroitin sulfate 1 domain and the chondroitin sulfate 2 domain. The carboxyl terminus of this peptide appeared to be the same as that of the proteolytically degraded aggrecan core protein, which is retained within the extracellular matrix of the tissue. Another two aggrecan fragments recovered from the medium of explant cultures with amino-terminal sequences in the chondroitin sulfate 2 domain at Ala¹⁷⁷² and Leu¹⁸⁷² were shown to have their carboxyl termini within the G3 globular domain. These results suggest that the catabolism of aggrecan between residues Glu³⁷³ and Ala³⁷⁴ in the interglobular domain by the putative proteinase, aggrecanase, may be dependent on prior proteolytic processing within the carboxyl-terminal region of the core protein.

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Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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