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

TitleExpression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation
Authors
KeywordsADAMTS-4
Issue Date2009
Citation
Rheumatology International, 2009, v. 29, n. 5, p. 525-534 How to Cite?
AbstractThe 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. © 2008 Springer-Verlag.
Persistent Identifierhttp://hdl.handle.net/10722/228069
ISSN
2015 Impact Factor: 1.702
2015 SCImago Journal Rankings: 0.638

 

DC FieldValueLanguage
dc.contributor.authorCheung, Kelvin S C-
dc.contributor.authorHashimoto, Ko-
dc.contributor.authorYamada, Norikazu-
dc.contributor.authorRoach, Helmtrud I.-
dc.date.accessioned2016-08-01T06:45:06Z-
dc.date.available2016-08-01T06:45:06Z-
dc.date.issued2009-
dc.identifier.citationRheumatology International, 2009, v. 29, n. 5, p. 525-534-
dc.identifier.issn0172-8172-
dc.identifier.urihttp://hdl.handle.net/10722/228069-
dc.description.abstractThe 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. © 2008 Springer-Verlag.-
dc.languageeng-
dc.relation.ispartofRheumatology International-
dc.subjectADAMTS-4-
dc.titleExpression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00296-008-0744-z-
dc.identifier.pmid18941754-
dc.identifier.scopuseid_2-s2.0-61449135868-
dc.identifier.volume29-
dc.identifier.issue5-
dc.identifier.spage525-
dc.identifier.epage534-
dc.identifier.f1000725822264-

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