Abstract
We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12–22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n = 6049), early progression (n = 4893), and late progression (n = 5078) of disease, with the preponderance being up-regulated. Additionally, 1918 genes were altered in expression with disease resolution, skewed towards down-regulation. Assessment of the genes demonstrated specific profiles of epithelial, bone/connective tissue, apoptosis/autophagy, metabolism, regulatory, immune, and inflammatory responses that were related to health, stages of disease, and tissues with resolved lesions. Unique transcriptomic profiles occured during the kinetics of the periodontitis lesion exacerbation and remission. We delineated phase specific gene expression profiles of the disease lesion. Detection of these gene products in gingival crevicular fluid samples from human disease may contribute to a better understanding of the biological dynamics of the disease to improve patient management.
Highlights
This report describes longitudinal studies of biological processes of periodontitis using a nonhuman primate model of ligature-induced disease
It is well recognized that periodontitis is generally not expressed until about the 3rd–4th decade of life, even though the host response system and oral microbiome are interacting during a 30 + year time period prior to d isease[20,21,22]
Based upon the biology of how a host reacts to a bacterial challenge, this initial insult would likely last for days or weeks, either resolving rapidly or transiting to progressing disease. It is unknown regarding the temporal linkage of the biological changes with detectable clinical disease, but it would be predicted that this interaction occurs with disease progression over weeks to months based upon rodent and nonhuman primate experimental data[9,10,28]
Summary
This report describes longitudinal studies of biological processes of periodontitis using a nonhuman primate model of ligature-induced disease. Gene expression profiles were determined in gingival tissues with health and during initiation, progression, and resolution of periodontitis, reflecting the episodic nature of the disease in humans. The findings would shed some light into the temporal nature of changes in biological factors/ pathways through the disease process. This would provide the potential for identifying targeted biomolecules that could be used to better characterize disease sites in humans, and identify differences in the biological characteristics of healthy (never diseased) sites from previously diseased sites that have been successfully treated, as potential biomarkers of future risk for disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
