Host metalloproteinases in Lyme arthritis

Objective: To assess the role of matrix metalloproteinases (MMPs) in cartil age and bone erosions in Lyme arthritis Methods. We examined synovial fluid from 10 patients with Lyme arthritis fo r the presence of MMP-2, MMP-3, MMP-9, and "aggrecanase" activity using gel atinolytic zymography and immunoblot analysis. We developed an in vitro mod el of Lyme arthritis using cartilage explants and observed changes in carti lage degradation in the presence of Borrelia burgdorferi and/or various pro tease inhibitors. Results. Synovial fluid from patients with Lyme arthritis was found to cont ain at least 3 MMPs: gelatinase A (MMP-2), stromelysin (MMP-3), and gelatin ase B (MMP-9). In addition, there was evidence in 2 patients of "aggrecanas e" activity not accounted for by the above enzymes. Infection of cartilage explants with B burgdorferi resulted in induction of MMP-3, MMP-9, and "agg recanase" activity. Increased induction of these enzymes by B burgdorferi a lone was not sufficient to cause cartilage destruction in the explants as m easured by glycosaminoglycan (GAG) and hydroxyproline release. However, add ition of plasminogen, which can act as an MMP activator, to cultures result ed in significant GAG and hydroxyproline release in the presence of B burgd orferi. The MMP inhibitor batimastat significantly reduced the GAG release and completely inhibited the collagen degradation. Conclusion. MMPs are found in synovial fluids from patients with Lyme arthr itis and are induced from cartilage tissue by the presence of B burgdorferi . Inhibition of MMP activity prevents B burgdorferi-induced cartilage degra dation in vitro.