arthritis-hands-epigenetics

Arthritis is a widespread, debilitating disease characterized by inflammation of the joints. It affects at least 52 million adults in the United States – that’s more than 1 out of every 5 people, according to the CDC. Although medication has improved in recent years, the diversity in pathogenic pathways in certain types of arthritis, for example, rheumatoid arthritis (RA), makes it difficult to pinpoint and alleviate pain in specific joints. Often times, clinical trials for drug treatments focus on alleviating the disease as a whole and may often overlook pain that fails to subside in particular joints. New research published in Nature Communications has found that key differences in epigenetic signatures in various arthritic joints in the body – in this case, knees and hips – could be the key to understanding the imbalance of treatment efficacy.

In this study, an international team of researchers from California, Pennsylvania, and China found differences in molecular signatures, specifically between DNA methylation marks, and cellular processes among two different types of arthritis – rheumatoid arthritis and osteoarthritis (OA). More surprisingly, these differences were also found between joint types. This could help explain why one targeted therapy for arthritis might work for knees but not for hips.

The most common type of, osteoarthritis, is characterized by damage to and ultimately the loss of cartilage, which cushions joints to allow them to move fluidly and without pain. Rheumatoid arthritis occurs when the body’s own immune system attacks its tissue. This autoimmune arthritis is capable of rapidly damaging joints. Before the development of viable therapy, patients with RA were often put in a wheelchair after just a few years. Additionally, there are differences in the types of joints affected by these two forms of arthritis. OA tends to arise in weight-bearing joints whereas RA is distributed symmetrically, often to the small joints of the wrists and hands. The reason behind when the diverse types of arthritis occurs, however, has remained largely unknown.

Professor in the departments of Chemistry and Biochemistry and Cellular and Molecular Medicine, Wei Wang, PhD, and professor in the Department of Medicine, Gary S. Firestein, MD from the University of California San Diego were co-corresponding authors of the study. They investigated the epigenetic patterns found in a specialized cell type that lines the inner part of the joints, called fibroblast-like synoviocytes (FLS).

“We hypothesized that changes in epigenetic modifications and gene expression between FLS in different joints might potentially contribute to differences in synovial inflammation and responses to clinical treatment,” Wang said.

The DNA methylation marks in the specialized cells lining the joints were significantly different in RA than in OA. DNA methylation is a well-known epigenetic mechanism that can impact gene expression via the attachment of methyl groups to specific locations on the DNA. Furthermore, the methylation marks varied depending on the joint – the knee or the hip. This suggests that the diversity of drug responses in people with RA may vary from joint to joint.

“We showed that the epigenetic marks vary from joint to joint in diseases like rheumatoid arthritis,” explained Firestein. “Even more importantly, the differences involved key genes and pathways that are designed to be blocked by new RA treatments. This might provide an explanation as to why some joints improve while others do not, even though they are exposed to the same drug.”

Firestein, the director of the Clinical and Translational Research Institute at UC San Diego, said their results can lead to potential new precision medicine approaches that target all joints and not just a single type. He also believes it has widespread implications for the evaluation of new drugs in trials.

Bailey Kirkpatrick

Source: Ai, R., Hammaker, D., Boyle, D.L., Morgan, R., Walsh, A.M., Fan, S., Firestein, G.S., Wang, W. (2016). Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes. Nature Communications, 7: 11849.

Reference: LaFee, S. Disjointed: Cell Differences May Explain Why Rheumatoid Arthritis Varies By Location. UC San Diego Health. 10 June 2016. Web.

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