Longitudinal evaluation of GCF MMP-3 and TIMP-1 levels as prognostic factors for progression of periodontitis

Background: To determine whether matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in gingival crevicular fluid (GCF) could serve as prognostic factors for the progression of periodontitis, we monitored GCF MMP-3 and TIMP-1 and periodontal status of selected sites in 40 medically healthy subjects over a 6-month period. Method: Clinical measurements including gingival index (GI), plaque index, bleeding on probing, suppuration, probing depth (PD), attachment loss (AL), and GCF samples were taken from 2 healthy sites (including sites with gingival recession, GI=0; PD less than or equal to3 mm; AL less than or equal to2 mm) and 2 periodontitis sites (GI greater than or equal to1;PD greater than or equal to5 mm; AL greater than or equal to3 mm) of each patient at baseline, 3-month and 6-month visits by means of sterile paper strips. GCF levels of MMP-3 and TIMP-1 were determined by sandwich ELISA assays. Results: The mean amounts of MMP-3 and TIMP-1 in diseased sites were significantly higher than in healthy sites (p<0.0001). Significantly higher GCF levels of MMP-3 and TIMP-1 were found at progressing sites than in nonprogressing periodontitis sites (0.001<p<0.01). A progressing site was defined as a site which had <greater than or equal to>2 mm loss of attachment during 6- month study period. GCF levels of MMP-3 were highly correlated with clinical measurements taken at baseline, 3-month and 6-month visits (p<0.001). TIMP-1 levels were only moderately correlated with probing depth acid attachment level (p<0.01). step-wise multiple regression analysis was performed to construct models for the prediction of probing depth and attachment loss increases. The most parsimonious regression models which had the best R-2 values included the following variables and accounted for the indicated % of variability. The regression model for the prediction of probing depth increase included MMP-3, smoking pack-years, TIMP-1 and accounted for 53% of the variability The best model for the prediction of attachment loss increase included MMP-3, smoking pack-years, age, TIMP-1 and explained 59% of the variability: Conclusion: These data indicate that sites with high GCF levels of MMP-3 and TIMP-1 are at significantly greater risk for progression of periodontitis.