A recent work in the Journal of Clinical Investigation highlights the role of lysosomal enzymes for protection against arthritis. Lysosomal enzyme beta-glucuronidase (GUSB) was found as a key regulator of arthritis severity associated to Lyme disease that is caused by the spirochete Borrelia burgdorferi, the most prevalent arthropod-borne illness in the United States. Severely arthritic C3H mice possessed a naturally occurring hypomorphic Gusb allele and C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. The hypomorph Gusb allele also exacerbated disease in a model of rheumatoid arthritis. Development of Lyme and rheumatoid arthritis in mice carrying the Gusb hypomorph allele was associated with heightened accumulation of GAGs in joint tissue. In summary, this work suggests that GUSB modulates severity of arthritis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue. Other lysosomal enzymes may have a similar effect on joint inflammation and therapies leading to increased expression of lysosomal enzymes in the joint might have potential for treatment of arthritis.
Posted by Nicola Brunetti-Pierri, MD