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Cellular and genetic processes vary in different joints in the body, explaining why treatments for rheumatoid arthritis and osteoarthritis sometimes work and sometimes don’t, according to a study announced Friday by the UC San Diego School of Medicine.

According to results published in the online edition of Nature Communications, Wei Wang, a professor in the departments of Chemistry and Biochemistry, and Cellular and Molecular Medicine at UCSD, and Dr. Gary Firestein, a professor in the Department of Medicine, investigated patterns that impact genetic expression in cells that line the inside of joints.

The researchers discovered that DNA methylation — a fundamental, life- long process in which a methyl group is added or removed from a DNA molecule to promote or suppress gene activity and expression — varies between the knees and hips of rheumatoid arthritis patients. A methyl group is a type of hydrocarbon.

“We showed that the epigenetic marks vary from joint to joint in diseases like rheumatoid arthritis,” Firestein said.

“Even more importantly, the differences involved key genes and pathways that are designed to be blocked by new RA treatments,” Firestein said. “This might provide an explanation as to why some joints improve while others do not, even though they are exposed to the same drug.”

At least 50 million adults and 300,000 children in this country have some type of arthritis, which includes more than 100 different diseases, according to the U.S. Centers for Disease Control and Prevention.

Osteoarthritis is the most common type and involves damage to and ultimately the loss of cartilage — the cushion inside joints that permits them to move smoothly and painlessly.

Rheumatoid arthritis is the most common chronic inflammatory arthritis and can rapidly damage joints. In the days before effective therapy was developed, the disease routinely put patients in a wheelchair after a few years.

Firestein said the study “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.”

Scientists from Janssen Research & Development in Pennsylvania and the University of Electronic Science and Technology in China also participated in the research, which was funded, in part, by the Rheumatology Research Foundation, Arthritis Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Science Foundation.

—City News Service

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