The University of Southampton
University of Southampton Institutional Repository

Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions

Roach, Helmtrud I., Yamada, Norikazu, Cheung, Kelvin S.C., Tilley, Simon, Clarke, Nicholas M.P., Oreffo, Richard O.C., Kokubun, Shoichi and Bronner, Felix (2005) Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions Arthritis & Rheumatism, 52, (10), pp. 3110-3124. (doi:10.1002/art.21300).

Record type: Article


Objective: To investigate whether the abnormal expression of matrix metalloproteinases (MMPs) 3, 9, and 13 and ADAMTS-4 by human osteoarthritic (OA) chondrocytes is associated with epigenetic unsilencing.
Methods: Cartilage was obtained from the femoral heads of 16 patients with OA and 10 control patients with femoral neck fracture. Chondrocytes with abnormal enzyme expression were immunolocalized. DNA was extracted, and the methylation status of the promoter regions of MMPs 3, 9, and 13 and ADAMTS-4 was analyzed with methylation-sensitive restriction enzymes, followed by polymerase chain reaction amplification.
Results: Very few chondrocytes from control cartilage expressed the degrading enzymes, whereas all clonal chondrocytes from late-stage OA cartilage were immunopositive. The overall percentage of nonmethylated sites was increased in OA patients (48.6%) compared with controls (20.1%): 20% versus 4% for MMP-13, 81% versus 47% for MMP-9, 57% versus 30% for MMP-3, and 48% versus 0% for ADAMTS-4. Not all CpG sites were equally susceptible to loss of methylation. Some sites were uniformly methylated, whereas in others, methylation was generally absent. For each enzyme, there was 1 specific CpG site where the demethylation in OA patients was significantly higher than that in controls: at -110 for MMP-13, -36 for MMP-9, -635 for MMP-3, and -753 for ADAMTS-4.
Conclusion: This study provides the first evidence that altered synthesis of cartilage-degrading enzymes by late-stage OA chondrocytes may have resulted from epigenetic changes in the methylation status of CpG sites in the promoter regions of these enzymes. These changes, which are clonally transmitted to daughter cells, may contribute to the development of OA.

Full text not available from this repository.

More information

Published date: October 2005
Organisations: Dev Origins of Health & Disease


Local EPrints ID: 25940
ISSN: 0004-3591
PURE UUID: fb7e367a-0c64-4495-a4c3-5c73f1f2a84c
ORCID for Richard O.C. Oreffo: ORCID iD

Catalogue record

Date deposited: 20 Apr 2006
Last modified: 17 Jul 2017 16:09

Export record



Author: Helmtrud I. Roach
Author: Norikazu Yamada
Author: Kelvin S.C. Cheung
Author: Simon Tilley
Author: Shoichi Kokubun
Author: Felix Bronner

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.