In what may prove to be a significant advance in the search for a treatment for osteoarthritis, scientists in the UK have discovered that people with osteoarthritis have a signature epigenetic change that is responsible for switching on and off a gene that produces a destructive enzyme called MMP13.
(Epigenetics is the study of heritable changes in gene expression or cellular phenotypes caused by mechanisms other than changes in the underlying DNA sequence.)
The enzyme, MMP13, is known to play a part in the destruction of joint cartilage. This makes MMP13 and the epigenetic changes that lead to its increased levels, prime targets for osteoarthritis drug development. The group’s finding was recently published in the FASEB Journal.
To make the discovery, David Young, Ph.D., of the Institute of Cellular Medicine at Newcastle University in Newcastle upon Tyne in the United Kingdom and colleagues compared the extent to which DNA methylation was different in cartilage from patients suffering from osteoarthritis and from healthy people of a similar age. They found that at one small position, the gene for MMP13 had less DNA methylation in diseased patients. Then they confirmed that reduced methylation of this gene increases levels of the destructive enzyme MMP13.
“As the population gets older, osteoarthritis presents increasing social and economic problems, ” said Young in the July 6 news release.
Our work provides a better understanding of the events that cause cartilage damage during osteoarthritis and provides hope that tailored drug development to prevent the progress of disease will improve the quality of life and mobility of many arthritis sufferers.
