Abstract
Although data describe the presence and increase of inflammatory mediators in the local environment in periodontitis vs. health in humans, details regarding how these responses evolve in the transition from health to disease, changes during disease progression, and features of a resolved lesion remain unknown. This study used a nonhuman primate model of ligature-induced periodontitis in young, adolescent, adult, and aged animals to document features of inflammatory response affected by age. Rhesus monkeys had ligatures tied and provided gingival tissue biopsy specimens at baseline, 0.5, 1, and 3 months of disease and at 5 months of the study, which was 2 months post-ligature removal for clinically resolved tissues. The transcriptome was assessed using microarrays for chemokine (n = 41), cytokine (n = 45), chemokine receptor (n = 21), cytokine receptor (n = 37), and lipid mediator (n = 31) genes. Limited differences were noted in healthy tissues for chemokine expression with age; however, chemokine receptor genes were decreased in young but elevated in aged samples. IL1A, IL36A, and IL36G cytokines were decreased in the younger groups, with IL36A elevated in aged animals. IL10RA/IL10RB cytokine receptors were altered with age. Striking variation in the lipid mediator genes in health was observed with nearly 60% of these genes altered with age. A specific repertoire of chemokine and chemokine receptor genes was affected by the disease process, predominated by changes during disease initiation. Cytokine/cytokine receptor genes were also elevated with disease initiation, albeit IL36B, IL36G, and IL36RN were all significantly decreased throughout disease and resolution. Significant changes were observed in similar lipid mediator genes with disease and resolution across the age groups. Examination of the microbiome links to the inflammatory genes demonstrated that specific microbes, including Fusobacterium, P. gingivalis, F. alocis, Pasteurellaceae, and Prevotella are most frequently significantly correlated. These correlations were generally positive in older animals and negative in younger specimens. Gene expression and microbiome patterns from baseline were distinctly different from disease and resolution. These results demonstrate patterns of inflammatory gene expression throughout the phases of the induction of a periodontal disease lesion. The patterns show a very different relationship to specific members of the oral microbiome in younger compared with older animals.
Document Type
Article
Publication Date
9-17-2021
Digital Object Identifier (DOI)
https://doi.org/10.3389/froh.2021.725115
Funding Information
This work was supported by National Institute of Health grant P20GM103538. We express our gratitude to the Caribbean Primate Research Center (CPRC) supported by grant P40RR03640, specifically Drs. Janis Gonzalez Martinez, Luis Orraca, and Armando Burgos, and the Center for Oral Health Research in the College of Dentistry at the University of Kentucky.
Related Content
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/metagenomics/, E-MTAB-1977 https://www.ncbi.nlm.nih.gov/, GSE180588.
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/froh.2021.725115/full#supplementary-material The material is also available for download as the additional file listed at the end of this record.
Repository Citation
Ebersole, Jeffrey L.; Nagarajan, Radhakrishnan; Kirakodu, Sreenatha S.; and Gonzalez, Octavio A., "Oral Microbiome and Gingival Gene Expression of Inflammatory Biomolecules with Aging and Periodontitis" (2021). Center for Oral Health Research Faculty Publications. 22.
https://uknowledge.uky.edu/cohr_facpub/22
Supplementary material: Data sheet
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Supplementary material: Image 1
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Supplementary material: Image 2
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Supplementary material: Image 3
Notes/Citation Information
Published in Frontiers in Oral Health, v. 2, article 725115.
© 2021 Ebersole, Nagarajan, Kirakodu and Gonzalez.
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