Rheumatoid arthritis affects up to 1.3% of people worldwide with a greater prevalence in women. It is a systemic autoimmune condition characterized by persistent inflammation of the synovial membrane that protects the joints. The most common ailments associated with rheumatoid arthritis are pain, redness and stiffness of the joints; however, the persistent inflammatory response can lead to erosion of the underlying cartilage and bone. Although there is no cure for rheumatoid arthritis, there are treatments to slow disease progression. New research by Sarah Headland at the London School of Medicine (London, UK) and colleagues has uncovered an important mechanism for preventing the erosion of cartilage that results from the immune response in joints, and this offers a potential new avenue for treating rheumatoid arthritis (Sci. Transl. Med. 7, 315ra190; 2015).

Treating cartilage diseases such as rheumatoid arthritis is challenging because the tissue is typically dense, avascular and impenetrable to cells. This makes the delivery of cartilage-protective agents nearly impossible. However these recent findings by Headland and colleagues show that neutrophils located in the synovial fluid surrounding cartilage secrete microvesicles that are capable of penetrating into cartilage through diffusion. Importantly, they found that when mice are unable to produce microvesicles, they develop advanced cartilage erosion. This demonstrates that microvesicle production is an important factor in maintaining healthy cartilage tissue, and manipulating the natural production of microvesicles could be a potential mechanism for treating persistent inflammation.

Credit: Suze777 /iStock/Thinkstock

Many immune cell-types, such as monocytes and T-cells, produce microvesicles; however, Headland and colleagues found that it is microvesicles from neutrophils that play a key role in promoting cartilage repair. These microvesicles carry anti-inflammatory cargo that, when delivered to cartilage cells, activates the expression of genes that protect cartilage. Using a murine model of arthritis, the group injected purified microvesicles into arthritic knee tissue to test the ability of these microvesicles to prevent cartilage degradation. By providing arthritic mice with microvesicles that contain this anti-inflammatory payload, they were able to significantly reduce the cartilage erosion caused by the inflammatory response.

Though the presence of neutrophil-derived microvesicles in arthritic human cartilage has not been directly tested, studies have confirmed the presence of neutrophil-derived proteins. Following on these other findings, the work by Headland et al. could provide a new therapeutic approach for treating prolonged and persistent joint inflammation.