Aggrecanase 1 May Play Key Role in Lyme Arthritis

Research provides model of how cartilage degradation occurs in Lyme arthritis

WEDNESDAY, Oct. 18 (HealthDay News) -- New research sheds light on how infection with Borrelia burgdorferi results in Lyme arthritis, and may help pave the way toward more effective cartilage-saving treatments. The report appears in the October issue of Arthritis & Rheumatism.

Aruna K. Behera, Ph.D., of the Tufts University School of Medicine in Boston, and colleagues found that B. burgdorferi infection induces aggrecanase 1 (ADAMTS-4) in human chondrocyte cell cultures. The active forms of ADAMTS-4 were increased in the synovial fluid of patients with Lyme arthritis and in the joints of mice infected with B. burgdorferi. Aggrecanase 2 (ADAMTS-5) was not induced in any of the models.

The researchers suspect that ADAMTS-4 cleaves aggrecan and exposes the joints' collagen matrix, allowing it to be processed by matrix metalloproteinases and resulting in cartilage degradation and destruction. Aggrecanases, not matrix metalloproteinases, seem to mediate the cleavage of aggrecan, based on bovine cartilage explants of this disease.

Thus, the "use of selective aggrecanase inhibitors may impart cartilage protection by preventing aggrecan degradation without some of the negative responses associated with more broad-spectrum matrix metalloproteinase inhibitors," the study authors conclude, noting that this will need to be investigated by future studies.

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