Transcriptomic analysis of gingival tissues in resolved experimental periodontal lesions of nonhuman primates

BACKGROUND: This study used a preclinical model of experimental periodontitis in nonhuman primates to evaluate the biological features of resolved periodontal lesions. METHODS: Macaca mulatta (rhesus monkeys) were age-stratified into young ≤3 years (7-10-year-old humans), adolescent/young adult 3-7 years (12-25-year-old), adults 12-15 years (40-50-year-old), and aged 17-23 years (60-80-year-old). The samples were also analyzed based on sex or matrilineal derivation. The gingival transcriptome was evaluated using microarray analyses on tissue biopsies from healthy tissues and at resolution (i.e., clinical improvement). RESULTS: Resolution sites showed clinical improvement, as well as patterns of increased or decreased gene expression in resolution versus healthy tissues in all age groups. These differences represented a large array of adaptive immune genes that were elevated in resolution, with decreased metabolic, regulatory, structural, and transcription factor gene expression in the resolution samples. Many of these genes were common to all age groups or sex/matriline, thus suggesting some fundamental core profile of affected genes that discriminate healthy from lesion resolution tissues. CONCLUSIONS: Irrespective of age, the biology of periodontal lesion resolution tissues is distinct from healthy tissues. Despite a robust inflammatory response to the ligature-induced microbiome changes during experimental periodontitis, younger individuals showed significantly less destructive disease and different transcriptome profiles that could reflect improved lesion resolution. While sex and matriline affected the gene expression patterns, these generally overlapped with the prominent genes identified for resolution versus health across age groups. Highly affected genes could be considered biomarkers for resolved tissues, linking clinical and biological resolution of periodontal lesions.