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Development of a neutralizing antibody specific for the active form of matrix metalloproteinase-13.

Abstract：

:Matrix metalloproteinase-13 (MMP-13) is important in the pathology of osteoarthritis (OA). Although MMP-13 is considered a therapeutic target for OA, it is unclear how MMP-13 activity is regulated by the system that comprises various proteinases and their inhibitors. MMP-13 neutralizing antibodies could be a useful tool for investigating the involvement of MMP-13 in cartilage degeneration in OA-affected joints because antibodies possess high affinity and specificity compared with low-molecular weight chemical compounds. On the basis of three-dimensional structure and amino acid sequence information on MMP-13, we selected an appropriate antigen peptide and generated a neutralizing antibody by immunizing mice with the antigen. The most significant property of monoclonal antibody 14D10 was the specific binding to the active form of MMP-13, but not to the latent form, or other MMPs. With this property, active MMP-13 was measured selectively by an enzyme-linked immunosorbet assay. Furthermore, 14D10 suppressed the cleavage of type II collagen in human articular chondrocyte cultures, and 14D10 is thought to inhibit MMP-13 activity effectively. Thus, the highly selective MMP-13 neutralizing antibody (14D10) might be a useful tool for investigating the mechanism of type II collagen degradation in arthritic pathology.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Naito S,Takahashi T,Onoda J,Yamauchi A,Kawai T,Kishino J,Yamane S,Fujii I,Fukui N,Numata Y

doi

10.1021/bi301228d

subject

Has Abstract

pub_date

2012-11-06 00:00:00

pages

8877-84

issue

44

eissn

0006-2960

issn

1520-4995

journal_volume

51

pub_type

杂志文章

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