Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119526

Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints.

M W Lark, E K Bayne, J Flanagan, C F Harper, L A Hoerrner, N I Hutchinson, I I Singer, S A Donatelli, J R Weidner, H R Williams, R A Mumford, and L S Lohmander

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Lark, M. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Bayne, E. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Flanagan, J. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Harper, C. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Hoerrner, L. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Hutchinson, N. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Singer, I. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Donatelli, S. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Weidner, J. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Williams, H. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Mumford, R. in: JCI | PubMed | Google Scholar

Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. michael_lark-1@sbphrd.com

Find articles by Lohmander, L. in: JCI | PubMed | Google Scholar

Published July 1, 1997 - More info

Published in Volume 100, Issue 1 on July 1, 1997
J Clin Invest. 1997;100(1):93–106. https://doi.org/10.1172/JCI119526.
© 1997 The American Society for Clinical Investigation
Published July 1, 1997 - Version history
View PDF
Abstract

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."

Version history
  • Version 1 (July 1, 1997): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts