IADR Abstract Archives
Transcriptomic Staging of Periodontitis Using the Nonhuman Primate Model
Objectives: Periodontitis is a chronic dysregulated response to a dysbiotic microbiome. The disease is expressed temporally as exacerbations and remissions with the frequency and magnitude of the episodes explaining the variation in disease extent/severity across the population. We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic changes that demarcated stages of periodontitis including initiation, progression, and resolution.
Methods: 18 adult M. macaca monkeys (12-22 yrs.) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained at baseline, 2 wks, 1 and 3 mo during periodontitis and at 5 mo reflecting clinical disease resolution. Gene expression was analyzed [Rhesus Gene 1.0 ST Array (Affymetrix)], data normalized, and two-tailed ttest performed.
Results: Baseline samples demonstrated 160 genes that were significantly different than their expression levels at each of the other time points (92↑;68↓). As would be expected a set of 2823 genes were altered from baseline to 2 weeks post-ligation (~80%↑). Expression of a pattern of 54 genes was altered uniquely at 2 wks (initiation) vs. all other time points. At the 1 mo (early progression) sampling only 4 genes were significantly different from other time points; however, by 3 mo (late progression), 51 other genes had changed significantly and profiled the disease process. Following clinical resolution (5 mo) 53 genes were altered in expression compared to all other time points, with the expression of 128 genes significantly different between the 5 mo resolved disease (“healthy”) and the baseline healthy tissues.
Conclusions: Unique transcriptomic profiles occur during the kinetics of periodontitis exacerbation and remission. Detection of the signals in human GCF samples may contribute to a better understanding of the biological dynamics of the disease, and as a future diagnostic tool to improve patient management.
Methods: 18 adult M. macaca monkeys (12-22 yrs.) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained at baseline, 2 wks, 1 and 3 mo during periodontitis and at 5 mo reflecting clinical disease resolution. Gene expression was analyzed [Rhesus Gene 1.0 ST Array (Affymetrix)], data normalized, and two-tailed ttest performed.
Results: Baseline samples demonstrated 160 genes that were significantly different than their expression levels at each of the other time points (92↑;68↓). As would be expected a set of 2823 genes were altered from baseline to 2 weeks post-ligation (~80%↑). Expression of a pattern of 54 genes was altered uniquely at 2 wks (initiation) vs. all other time points. At the 1 mo (early progression) sampling only 4 genes were significantly different from other time points; however, by 3 mo (late progression), 51 other genes had changed significantly and profiled the disease process. Following clinical resolution (5 mo) 53 genes were altered in expression compared to all other time points, with the expression of 128 genes significantly different between the 5 mo resolved disease (“healthy”) and the baseline healthy tissues.
Conclusions: Unique transcriptomic profiles occur during the kinetics of periodontitis exacerbation and remission. Detection of the signals in human GCF samples may contribute to a better understanding of the biological dynamics of the disease, and as a future diagnostic tool to improve patient management.