title: Development of a monoclonal anti-ADAMTS-5 antibody that specifically blocks the interaction with LRP1.
abstract: 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.
authors.affiliation: a Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford , Headington , Oxford , UK.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Santamaria
authors.affiliation: b Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford , Headington, Oxford , UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Fedorov
authors.affiliation: c IONTAS, Iconix Park , Pampisford, Cambridge , UK.
authors.forename: John
authors.initials: J
authors.lastname: McCafferty
authors.affiliation: d Cancer Research UK Cambridge Institute, Department of Oncology, University of Cambridge, Li Ka Shing Centre , Cambridge , UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
authors.affiliation: e Department of Clinical Sciences and Services , Royal Veterinary College, North Mymms , Hatfield , Herts , UK.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Dudhia
authors.affiliation: a Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford , Headington , Oxford , UK.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.affiliation: a Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford , Headington , Oxford , UK.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000071116:ADAMTS5 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D002417:Cattle; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D051379:Mice
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human
keywords: Aggrecanase; cartilage; endocytosis; extracellular matrix; proteoglycanase