| Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. | |
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MedLine Citation:
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PMID: 18941754 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Kelvin S C Cheung; Ko Hashimoto; Norikazu Yamada; Helmtrud I Roach |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-10-22 |
Journal Detail:
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Title: Rheumatology international Volume: 29 ISSN: 1437-160X ISO Abbreviation: Rheumatol. Int. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-26 Completed Date: 2009-09-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8206885 Medline TA: Rheumatol Int Country: Germany |
Other Details:
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Languages: eng Pagination: 525-34 Citation Subset: IM |
Affiliation:
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Bone and Joint Research Group, IDS Building, MP887, General Hospital, University of Southampton, Southampton, UK. karatekelvin@gmail.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
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genetics,
metabolism* Aged Aged, 80 and over Cartilage, Articular / metabolism* Chondrocytes / metabolism*, pathology DNA Methylation Epigenesis, Genetic Female Fluorescent Antibody Technique, Indirect Gene Expression Regulation, Enzymologic Humans Immunohistochemistry Male Osteoarthritis / genetics*, metabolism* Procollagen N-Endopeptidase / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/aggrecanase-1; EC 3.4.24.14/Procollagen N-Endopeptidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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