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

MAbs. 2017 May/Jun;9(4):595-602. doi: 10.1080/19420862.2017.1304341. Epub 2017 Mar 17.

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.

Keywords: Aggrecanase; cartilage; endocytosis; extracellular matrix; proteoglycanase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAMTS5 Protein* / antagonists & inhibitors
  • ADAMTS5 Protein* / metabolism
  • Animals
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Cattle
  • Chondrocytes / cytology
  • Chondrocytes / metabolism*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Mice

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • ADAMTS5 Protein
  • ADAMTS5 protein, human