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DNA Methylation in Osteoarthritis

[ Vol. 16 , Issue. 6 ]

Author(s):

Wouter den Hollander and Ingrid Meulenbelt   Pages 419 - 426 ( 8 )

Abstract:


Osteoarthritis (OA) is a prevalent disease of articular joints and primarily characterized by degradation and calcification of articular cartilage. Presently, no effective treatment other than pain relief exists and patients ultimately need to undergo replacement surgery of the affected joint. During disease progression articular chondrocytes, the single cell type present in articular cartilage, show altered transcriptional profiles and undergo phenotypic changes that resemble the terminal differentiation route apparent in growth plate chondrocytes. Hence, given its prominent function in both regulating gene expression and maintaining cellular phenotypes, DNA methylation of CpG dinucleotides is intensively studied in the context of OA. An increasing number of studies have been published that employed a targeted approach on genes known to play a role in OA pathophysiology. As of such, it has become clear that OA responsive DNA methylation changes seem to mediate disease associated aberrant gene expression. Furthermore, established OA susceptibility alleles such as GDF5 and DIO2 appear to confer OA risk via DNA methylation and respective pathophysiological expression changes. In more recent years, genome wide profiling of DNA methylation in OA affected articular cartilage has emerged as a powerful tool to address the epigenetic changes in their entirety, which has resulted in the identification of putative patient subgroups as well as generic OA associated pathways.

Keywords:

Articular cartilage, Data integration, DNA methylation, Osteoarthritis, Transcriptomics.

Affiliation:

Dept. Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Center, LUMC Post-zone S-05-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

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