Wondering Why RA Treatments Only Work on Certain Joints? DNA Methylation May Hold an Answer

Wondering Why RA Treatments Only Work on Certain Joints? DNA Methylation May Hold an Answer

DNA methylation, a biological mechanism that controls which genes will be expressed and which ones will be silenced in different cells, varies between the cells lining the inside of different joints in patients with rheumatoid arthritis (RA), a new study shows. This finding could explain why an RA drug that is effective on knee joints doesn’t treat the hips joints, and vice versa, and may be of use in developing better treatments targeting specific joints in patients.

Dr. Gary Firestein, of the Department of Medicine University of California, San Diego, said in a press release that the work “opens up the potential for precision medicine approaches that allow us to target all of the joints, not just a subset. It has broad implications for how we evaluate new drugs in clinical trials as well.”

The researchers showed that the epigenetic, or methylation, patterns are different between joints in diseases like RA. In addition they showed that there are distinct differences in key cellular processes and molecular signatures among the different types of arthritis that affects different joints in the body. Most RA treatments are designed to block these genes and pathways, providing a possible reason why the same drug may improve some joints while having no effect on others.

“Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint,” the research team wrote.

The results of the study, “Joint-specific DMA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes,” will be published in the June 10 online issue of Nature CommunicationsIt was a collaborative effort among researchers in California, Pennsylvania, and China.

According to the Centers for Disease Control and Prevention, there are at least 50 million adults and 300,000 children in the U.S. who have some type of arthritis. Osteoarthritis (OA) is the most common type and causes damage to cartilage, while RA is the most common chronic inflammatory arthritis and also affects joints.

Interestingly, the two conditions affect different parts of the body. OA localizes more in weight-bearing joints such as the hips, while RA starts more in the small joints, such as the ones of the hands and wrists, and spreads to larger weight-bearing joints. To date, the reason behind these differences are not clear. This research might shed light on what causes them.

DNA methylation is a fundamental biological process where a methyl group is added to or removed from DNA, controlling whether or not certain genes will be translated or “read.” It is a key process involved in development, aging, and cancer.

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