Mechanism of catabolism of aggrecan by articular cartilage.
Characterization of aggrecan core protein peptides appearing in the medium of adult articular cartilage maintained in tissue culture showed that eight major peptides could be detected. The two largest peptides had the same N-terminal sequence as bovine aggrecan core protein and probably represent partly degraded aggrecan lost to the medium in the form of the proteoglycan aggregate. The three next smallest peptides were all shown to have another N-terminal sequence which corresponded to a sequence in the interglobular domain starting at alanine residue 393 of the human aggrecan core protein (K. Doege et al., 1991, J. Biol. Chem. 266, 894-902). Two other peptides were isolated and shown to have two different N-terminal amino sequences corresponding to sequences in the chondroitin sulfate attachment domain 2 of the core protein starting at alanine residue 1839 and leucine residue 1939 of human aggrecan. This suggests that the catabolism of aggrecan by adult articular cartilage occurs by the proteolytic cleavage of the core protein of this proteoglycan at three separate sites. Examination of the amino acid sequences around each of these cleavage sites showed a similar pattern TEGE decreases ARGS, TAQE decreases AGEG, and VSQE decreases LGQR, suggesting that a single proteinase may be involved in the catabolism of aggrecan. Analysis of synovial fluids and serum of age-matched animals revealed the presence of aggrecan core protein peptides corresponding in size to those detected in vitro, thus indicating the cleavage observed in explant culture is the same as that which occurs in vivo.
Ilic
M Z
MZ
Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
Handley
C J
CJ
Robinson
H C
HC
Mok
M T
MT
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D002808:Chondroitin Lyases / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D046508:Culture Techniques; D010450:Endopeptidases / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006026:Glycoside Hydrolases; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry; D001616:beta-Galactosidase / Q000378:metabolism
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans; D006026:Glycoside Hydrolases; C026093:keratan-sulfate endo-1,4-beta-galactosidase; D001616:beta-Galactosidase; D010450:Endopeptidases; D002808:Chondroitin Lyases