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Development of a monoclonal anti-ADAMTS-5 antibody that specifically blocks the interaction with LRP1

The potent aggrecanase ADAMTS-5 is constitutively secreted by chondrocytes, but it is rapidly endocytosed in normal cartilage via the cell surface endocytic receptor LRP1. Therefore it is difficult to detect the total ADAMTS-5 activity produced. In this study, we isolated a monoclonal anti-ADAMTS-5...

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Detalles Bibliográficos
Autores principales: Santamaria, Salvatore, Fedorov, Oleg, McCafferty, John, Murphy, Gillian, Dudhia, Jayesh, Nagase, Hideaki, Yamamoto, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419085/
https://www.ncbi.nlm.nih.gov/pubmed/28306378
http://dx.doi.org/10.1080/19420862.2017.1304341
Descripción
Sumario:The potent aggrecanase ADAMTS-5 is constitutively secreted by chondrocytes, but it is rapidly endocytosed in normal cartilage via the cell surface endocytic receptor LRP1. Therefore it is difficult to detect the total ADAMTS-5 activity produced. In this study, we isolated a monoclonal anti-ADAMTS-5 antibody 1B7 that blocks LRP1-mediated internalization without affecting the aggrecanolytic activity. Addition of 1B7 to cultured human chondrocytes revealed the full aggrecanolytic activity of ADAMTS-5 generated by the cells. 1B7 is a useful tool to estimate the ADAMTS-5 activity and to identify its potential roles in the tissues.