DNA Methylation, Chondrogenesis, and Cartilage Degeneration
Pia Margarethe Gebhard,
Helmtrud I. Roach.
In the last few years there has been an explosion of research into epigenetics and, in particular, the roles of DNA methylation in the normal functioning of the mammalian organism as well as whether changes in methylation status contribute to or cause aberrant gene expression in diseases. While abnormal patterns of DNA methylation in cancer cells have been intensively investigated, little attention has so far been paid to the role of DNA methylation in cartilage and cartilage degeneration. This review summarizes the current knowledge of the mechanism of methylation, its association with transcriptional silencing, possible mechanisms of hyper- and hypomethylation as well as age- and disease related changes in methylation pattern. We discuss the possible involvement of DNA methylation in chondrogenesis as well as its potential importance for cartilage degradation. Overall, epigenetic gene regulation has largely been neglected in cartilage research, but is likely to be an important issue in future. There is increasing evidence that besides cytokines, growth factors and changes in matrix composition, variations in the genetic methylation pattern might also be important determinators of the complex gene expression pattern pathognomically observed in osteoarthritic cartilage tissue.
Keywords: CpG-elements, DNA methyltransferases, transcriptional repression domain (TRD), BMP-signaling system, Osteoarthritis
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