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Immune system transcriptome in gingival tissues of young nonhuman primates.

ABSTRACT: Young/adolescent humans harbor many microorganisms associated with periodontal disease in adults and show substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft- and hard-tissue destruction that hallmark periodontitis.This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (< 3 years of age) compared with older animals (5-23 years of age). RNA was isolated from the tissues and analyzed for the transcriptome using the Rhesus Macaque GeneChip (Affymetrix).Global transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed across at least one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes was identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A principal components analysis created metagenes of expression profiles for classifying the 23 animals.The results provide novel system-level insights into gene-expression differences in gingival tissues from healthy young animals, weighted toward host responses associated with anti-inflammatory biomolecules or those linked with T-cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent 'resistance' of younger individuals to developing periodontal disease.

SUBMITTER: Gonzalez OA

PROVIDER: S-EPMC4681702 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Immune system transcriptome in gingival tissues of young nonhuman primates.

Gonzalez O A OA Nagarajan R R Novak M J MJ Orraca L L Gonzalez-Martinez J A JA Kirakodu S S SS Ebersole J L JL

Journal of periodontal research 20150616 2

<h4>Background and objective</h4>Young/adolescent humans harbor many microorganisms associated with periodontal disease in adults and show substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft- and hard-tissue destruction that hallmark periodontitis.<h4>Material and methods</h4>This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (< 3 years of age) compared with older animals ...[more]

PMID: 26077888

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Project description:Background and objectiveBiallelic loss-of-function mutations of human FAM20A have been known to cause enamel-renal syndrome (ERS), featured by agenesis of dental enamel, nephrocalcinosis, and other orodental abnormalities, including gingival hyperplasia. However, while the histopathology of this gingival anomaly has been analyzed, its underlying molecular mechanism remains largely unknown. This study aimed to unravel the pathogenesis of gingival hyperplasia in ERS.MethodsWhole-exome sequencing was conducted for an ERS case. Transcriptome analyses, using RNA sequencing, of the patient's gingiva were performed to unravel dysregulated molecules and aberrant biological processes underlying the gingival pathology of ERS, which was further confirmed by histology and immunohistochemistry.ResultsTwo novel frameshift FAM20A mutations in Exon 1 (g.5417delG; c.129delG; p.Cys44Alafs*101) and Exon 5 (g.62248_62249delAG; c.734_735delAG; p.Glu245Glyfs*11) were identified. Transcriptional profiling of patient's gingival tissue revealed a total of 1683 genes whose expression had increased (1129 genes) or decreased (554 genes) at least 2-fold compared to control gingival tissues. There were 951 gene ontology (GO) terms of biological process being significantly over-represented or under-represented. While GOs involved in extracellular matrix organization, angiogenesis, biomineralization, and epithelial cell proliferation appeared to be activated in ERS gingiva, genes related to keratinocyte differentiation, epithelial development, and keratinization were of decreased expression. FAM20A immunohistochemistry revealed a strong reactivity at the suprabasal layers of epithelium in control gingiva but showed a significantly diminished and scattered signal in ERS tissues. For genes showing significant over-expression in the transcriptome analyses, namely ALPL, SPARC, and ACTA2, an increased immunoreactivity was observed.ConclusionOur results unraveled a potential role for FAM20A in homeostasis of both gingival epithelium and connective tissues.

Dataset Information

Immune system transcriptome in gingival tissues of young nonhuman primates.

Publications

Immune system transcriptome in gingival tissues of young nonhuman primates.

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