Development of a Neutralizing Antibody Specific for the Active Form of Matrix Metalloproteinase-13

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• 作者：Shoichi Naito ; Tatsuya Takahashi ; Junji Onoda ; Akira Yamauchi ; Taeko Kawai ; Junji Kishino ; Shoji Yamane ; Ikuo Fujii ; Naoshi Fukui ; Yoshito Numata
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：November 6, 2012
• 年：2012
• 卷：51
• 期：44
• 页码：8877-8884
• 全文大小：329K
• 年卷期：v.51,no.44(November 6, 2012)
• ISSN：1520-4995

文摘

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.