DNA methylation in osteoarthritic chondrocytes: a new molecular target.
OBJECTIVE
To review the current knowledge of the mechanism of DNA methylation, its association with transcriptional silencing, possible mechanisms of hyper- and hypomethylation and how epigenetic changes may relate to the pathogenesis of osteoarthritis (OA).


METHODS
Journal literature was searched using Pubmed. Since there are very few publications directly on epigenetic phenomena in OA, the search was extended to give an overview of epigenetic mechanisms as they relate to the molecular mechanisms of the disease.


RESULTS
While the epigenetics of cancer cells have been intensively investigated, little attention has so far been paid as to whether epigenetic changes contribute to the pathology of non-neoplastic diseases such as OA. This review explains the mechanisms of DNA methylation, its role in transcriptional regulation, and possible demethylation mechanisms that may be applicable to OA. Preliminary evidence suggests that changes in DNA methylation, together with cytokines, growth factors and changes in matrix composition, are likely to be important in determining the complex gene expression patterns that are observed in osteoarthritic chondrocytes.


CONCLUSIONS
Early evidence points to a role of epigenetics in the pathogenesis of OA. Since epigenetic changes, although heritable at the cellular level, are potentially reversible, epigenetics could be a new molecular target for therapeutic intervention, especially early in the disease.
Roach
H I
HI
Bone and Joint Research Group, Division of Developmental Origins of Health and Disease, University of Southampton, UK. hr@soton.ac.uk
Aigner
T
T
D019902:Chondrocytes / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism