Expression levels of matrix metalloproteinase (MMP)-9 and its specific inhibitor TIMP-1, in septic and aseptic arthritis of the knee.

ABSTRACT

PURPOSE: In cases of septic knee arthritis, there is excess of matrix metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs), due to enhanced expression and activation that are induced by bacteria in comparison with rheumatic or degenerative arthritis. The aim of this study was to explore the expression levels of synovial gelatinase MMP-9 and its specific inhibitor TIMP-1 in septic and aseptic arthritis and their potential use as additional aids to clinical investigation. METHODS: Gelatin zymography and western blot analysis were applied in effusions from knees of the patients with septic (SA-10 patients), rheumatic (RA-10 patients) and osteoarthritis (OA-10 patients). RESULTS: Zymographic analysis revealed that all samples contained latent MMP-2 activity, albeit activated MMP-2 appeared in more of the septic than aseptic effusions. MMP-9 was not detected in osteoarthritic synovial fluid samples. Only trace amounts of MMP-9 activity were detected in 4 of 10 patients with RA, whereas higher MMP-9 levels were evident in all samples from SA (P = 0.0241). In immunoblotting assays, samples from SA showed significantly higher levels of MMP-9 compared with samples from RA (P = 0.0052), confirming zymographic results. Although no significant difference in TIMP-1 levels was observed, the estimated MMP-9/TIMP-1 ratio of septic effusions was significantly higher compared with aseptic ones (P = 0.0029). CONCLUSIONS: The data presented suggest enhanced expression and activation of MMP-9 in septic native knee arthritis compared with aseptic. The presence of high levels of MMP-9 with concomitantly increased MMP-9/TIMP-1 ratio and activated gelatinases in effusions, independent of neutrophilic counts, may be indicative for infection.