Contribution of Matrix Metalloproteinase 2 to Joint Destruction in Group B Streptococcus-Induced Murine Arthritis

Objective. To assess the role of matrix metalloproteinase 2 (MMP-2) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice. Methods. Mice deficient in MMP-2 (MMP-2(-/-)) and wild-type controls were injected intravenously with 1 x 10(7) colony-forming units of type IV GBS (strain 1/82). Levels of MMP-2, mortality rates, evolution of arthritis, bacterial clearance, joint histopathologic features, and production of cytokines and chemokines were examined in both experimental groups of mice on days 3, 6, and 9 after infection. Results. MMP-2 was produced during GBS infection. Disruption of the gene for MMP-2 resulted in a decrease in the incidence and severity of arthritis, as demonstrated by both clinical and histologic findings, without affecting mortality rates. Amelioration of arthritis was accompanied by a dramatic reduction in the local production of interleukin-1 beta (IL-1 beta), IL-6, macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-2 and a reduced bacterial burden. Conclusion. MMP-2, produced early during GBS infection in mice, is involved in the degradation of extracellular matrix components at the level of the joint. This degradation is the first step in a cascade of events (joint invasion by GBS, extravasation and accumulation of inflammatory cells, proinflammatory cytokine production), all of which contribute to the damage of articular tissue. Thus, MMP-2 should be regarded as a potential therapeutic target in GBS-induced arthritis.