eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2008   Volume No 15 – pages 11- 26

Title: ADAMTS-5: The story so far

Author: AJ Fosang, FM Rogerson, CJ East, H Stanton

Address: University of Melbourne Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia

E-mail: amanda.fosang at

Key Words: Aggrecanase, ADAMTS-5, ADAMTS-4, aggrecanolysis, metalloproteinase, cartilage, arthritis

Publication date: February 5th 2008

Abstract: The recent discovery of ADAMTS-5 as the major aggrecanase in mouse cartilage came as a surprise. A great deal of research had focused on ADAMTS-4 and much less was known about the regulation, expression and activity of ADAMTS-5. Two years on, it is still not clear whether ADAMTS-4 or ADAMTS-5 is the major aggrecanase in human cartilage. On the one hand there are in vitro studies using siRNA, neutralising antibodies and immunoprecipitation with anti-ADAMTS antibodies that suggest a significant role for ADAMTS-4 in aggrecanolysis. On the other hand, ADAMTS-5(but not ADAMTS-4)-deficient mice are protected from cartilage erosion in models of experimental arthritis, and recombinant human ADAMTS-5 is substantially more active than ADAMTS-4. The activity of both enzymes is modulated by C-terminal processing, which occurs naturally in vivo. The most interesting finding to emerge from our comparison of ADAMTS-5 and ADAMTS-4 is that in terms of gene regulation, these two enzymes are the antitheses of each other. In most cases, ADAMTS-5 is constitutively expressed in human chondrocytes and synovial fibroblasts, whereas ADAMTS-4 expression is induced by proinflammatory cytokines. This paper reviews the data on ADAMTS-5 so far. It represents a snapshot in time of a field that is fast-moving and very exciting.


Article download: Pages 11-26 (PDF file)

Acrobat Reader:

To read this article you will need to install Adobe Acrobat Reader on your computer. Should you experience any difficulty in reading the PDF file we suggest that you save the file to your computer BEFORE opening it from Adobe Acrobat.