Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)

FEBS Letters

Stracke, Jan O.¹  Last, Karena⁴  Fosang, Amanda J.⁴  Murphy, Gillian¹  Llano, Elena⁵  Mercuri, Francesca A.⁴  Di Cesare, Paul E.²  Pendás, Alberto M.⁵  Perris, Roberto³  Knäuper, Vera¹ 

[1] School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK;Musculoskeletal Research Centre, Department of Orthopaedic Surgery, New York University-Hospital for Joint Diseases, New York, NY 10003, USA;Department of Evolutionary and Functional Biology, University of Parma, 43100 Parma, Italy;Orthopaedic Molecular Biology Research Unit, University of Melbourne, Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Vic. 3052, Australia;Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, 33006 Oviedo, Spain

关键词: Aggrecan;    Proteoglycan;    Matrix metalloproteinase;    Cartilage oligomeric matrix protein;    Matrix metalloproteinase-19;    Matrix metalloproteinase-20;    MMP;    matrix metalloproteinase;    IGD;    inter-globular domain;    COMP;    cartilage oligomeric matrix protein;    ECM;    extracellular matrix;    RA;    rheumatoid arthritis;    OA;    osteoarthritis;   

DOI  :  10.1016/S0014-5793(00)01819-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Asn³⁴¹ and Phe³⁴², 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.

【 授权许可】

Unknown