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Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation

Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation
Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation
The two major aggrecanases involved in osteoarthritis (OA) are ADAMTS-4 and ADAMTS-5. Knock-out studies suggested that ADAMTS-5, but not ADAMTS-4, is the major aggrecanase in murine OA. However, studies of human articular cartilage suggest that ADAMTS-4 also contributes to aggrecan degradation in human OA. This study investigated ADAMTS-4 in human OA. While ADAMTS-4 was virtually absent in control cartilage, numerous ADAMTS-4 immuno-positive chondrocytes were present in OA cartilage and their numbers increased with disease severity. RT-PCR confirmed expression, especially in the surface zone. DNA methylation was lost at specific CpG sites in the ADAMTS-4 promoter in OA chondrocytes, suggesting that the increased gene expression was more than a simple up-regulation, but involved loss of DNA methylation at specific CpG sites, resulting in a heritable and permanent expression of ADAMTS-4 in OA chondrocytes. These results suggest that ADAMTS-4 is epigenetically regulated and plays a role in aggrecan degradation in human OA
gene expression, chondrocytes, osteoarthritis, bone, gene-expression, expression, dna methylation, human, disease, up-regulation
0172-8172
525-534
Cheung, K. S.
0054d827-b15a-441f-9c67-77361d6daf34
Hashimoto, K.
4589dbf6-e5a6-429d-b5cd-c348f88d6c40
Yamada, N.
11a3085c-3748-4222-9c5e-52dfc8b08ecb
Roach, H. I.
7c14aee8-fcc9-4589-95d7-b2af351e99a4
Cheung, K. S.
0054d827-b15a-441f-9c67-77361d6daf34
Hashimoto, K.
4589dbf6-e5a6-429d-b5cd-c348f88d6c40
Yamada, N.
11a3085c-3748-4222-9c5e-52dfc8b08ecb
Roach, H. I.
7c14aee8-fcc9-4589-95d7-b2af351e99a4

Cheung, K. S., Hashimoto, K., Yamada, N. and Roach, H. I. (2008) Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatology international, 29 (5), 525-534. (doi:10.1007/s00296-008-0744-z).

Record type: Article

Abstract

The two major aggrecanases involved in osteoarthritis (OA) are ADAMTS-4 and ADAMTS-5. Knock-out studies suggested that ADAMTS-5, but not ADAMTS-4, is the major aggrecanase in murine OA. However, studies of human articular cartilage suggest that ADAMTS-4 also contributes to aggrecan degradation in human OA. This study investigated ADAMTS-4 in human OA. While ADAMTS-4 was virtually absent in control cartilage, numerous ADAMTS-4 immuno-positive chondrocytes were present in OA cartilage and their numbers increased with disease severity. RT-PCR confirmed expression, especially in the surface zone. DNA methylation was lost at specific CpG sites in the ADAMTS-4 promoter in OA chondrocytes, suggesting that the increased gene expression was more than a simple up-regulation, but involved loss of DNA methylation at specific CpG sites, resulting in a heritable and permanent expression of ADAMTS-4 in OA chondrocytes. These results suggest that ADAMTS-4 is epigenetically regulated and plays a role in aggrecan degradation in human OA

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More information

Published date: 2008
Keywords: gene expression, chondrocytes, osteoarthritis, bone, gene-expression, expression, dna methylation, human, disease, up-regulation

Identifiers

Local EPrints ID: 70329
URI: https://eprints.soton.ac.uk/id/eprint/70329
ISSN: 0172-8172
PURE UUID: 3035f132-b75f-441d-ab9e-c8fc26dc28fc

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Date deposited: 02 Feb 2010
Last modified: 19 Jul 2017 00:04

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