Degradation of cartilage aggrecan by collagenase-3 (MMP-13)

• Published in: FEBS letters Vol. 380; no. 1; pp. 17 - 20
• Main Authors: Fosang, Amanda J., Last, Karena, Knäuper, Vera, Murphy, Gillian, Neame, Peter J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 12-02-1996
• Subjects: 4-aminophenylmercuric acetate; [4-(2-aminoethyl)benzene]sulfonylfluoride; AEBSF; Aggrecan; Aggrecans; Amino Acid Sequence; Animals; APMA; Arthritis; Cartilage - metabolism; Cartilage degradation; Collagenase; Collagenases - metabolism; ECL; enhanced chemiluminescence; Enzyme Activation - drug effects; Extracellular Matrix Proteins; horseradish peroxidase; HRP; Humans; IGD; interglobular domain of aggrecan; Lectins, C-Type; Matrix metalloproteinase; Matrix Metalloproteinase 13; matrix metalloproteinases; MMPs; Molecular Sequence Data; PBS; Phenylmercuric Acetate - analogs & derivatives; Phenylmercuric Acetate - pharmacology; phosphate-buffered saline; Proteoglycans - metabolism; Sequence Analysis; Species Specificity; Substrate Specificity; Trypsin - pharmacology; PBS; AEBSF; IGD; MMPs; HRP; Collagenase; Arthritis; Aggrecan; Matrix metalloproteinase; APMA; Cartilage degradation; ECL
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)01539-6

Degradation of the large cartilage proteoglycan aggrecan in arthritis involves an unidentified enzyme aggrecanase, and at least one of the matrix metalloproteinases. Proteinase-sensitive cleavage sites in the aggrecan interglobular domain (IGD) have been identified for many of the human MMPs, as well as for aggrecanase and other proteinases. The major MMP expressed by chondrocytes stimulated with retinoic acid to degrade their matrix is collagenase-3 or MMP-13. Because of its potential role in aggrecan degradation we examined the specificity of MMP-13 for an aggrecan substrate. The results show that MMP-13 cleaves aggrecan in the IGD at the same site (..PEN
341-FFG..) identified for other members of the MMP family, and also at a novel site ..VKP
384-VFE.. not previously observed for other proteinases.