Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP).
Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. j.stracke@uea.ac.uk
J O
JO
Stracke
A J
AJ
Fosang
K
K
Last
F A
FA
Mercuri
A M
AM
Pendás
E
E
Llano
R
R
Perris
P E
PE
Di Cesare
G
G
Murphy
V
V
Knäuper
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002356:Cartilage / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein; D020134:Catalytic Domain; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type; D064235:Matrilin Proteins; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D013379:Substrate Specificity; D013552:Swine; D014070:Tooth / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
D053674:Aggrecans; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D037181:Lectins, C-Type; D064235:Matrilin Proteins; D010446:Peptide Fragments; D011509:Proteoglycans; D011994:Recombinant Proteins; C577553:TSP5 protein, human; C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19