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Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.

ABSTRACT: Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since ageing is a risk factor for periodontitis, we sought to identify age-related gingival transcriptome changes associated with bone metabolism in both healthy and in naturally occurring periodontitis.Adult (12-16 years) and aged (18-23 years) non-human primates (M. mulatta) (n = 24) were grouped into healthy and periodontitis. Gingival tissue samples were obtained and subjected to microarray analysis using the Gene Chip Macaque Genome Array. Gene expression profiles involved in osteoclast/osteoblast proliferation, adhesion and function were evaluated and compared across and between the age groups. QPCR was also performed on selected genes to validate microarray data.Healthy aged tissues showed a gene profile expression that suggest enhancement of osteoclastic adhesion, proliferation/survival and function (SPP1, TLR4, MMP8 and TFEC) and impaired osteoblastic activity (SMEK3P and SMAD5). The gingival transcriptome in both adult and aged animals with naturally occurring periodontitis (FOS, IL6, TLR4, MMP9, MMP10 and SPP1 genes) was consistent with a local inflammatory response driving towards bone/connective tissue destruction.A pro-osteoclastogenic gingival transcriptome is associated with periodontitis irrespective of age; however; a greater bone-destructive molecular environment is associated with ageing in healthy tissues.

SUBMITTER: Pandruvada SN

PROVIDER: S-EPMC4844783 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.

Pandruvada Subramanya N SN Gonzalez Octavio A OA Kirakodu Sreenatha S Gudhimella Sudha S Stromberg Arnold J AJ Ebersole Jeffrey L JL Orraca Luis L Gonzalez-Martinez Janis J Novak Michael J MJ Huja Sarandeep S SS

Journal of clinical periodontology 20160406 5

<h4>Aim</h4>Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since ageing is a risk factor for periodontitis, we sought to identify age-related gingival transcriptome changes associated with bone metabolism in both healthy and in naturally occurring periodontitis.<h4>Materials and methods</h4>Adult (12-16 years) and aged (18-23 years) non-human primates (M. mulatta) (n = 24) were grouped into healthy and periodontitis. Gingival tiss ...[more]

PMID: 26859687

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Project description:The epithelial barrier at mucosal sites comprises an important mechanical protective feature of innate immunity, and is intimately involved in communicating signals of infection/tissue damage to inflammatory and immune cells in these local environments. A wide array of antimicrobial factors (AMF) exist at mucosal sites and in secretions that contribute to this innate immunity. A non-human primate model of ligature-induced periodontitis was used to explore characteristics of the antimicrobial factor transcriptome (n = 114 genes) of gingival biopsies in health, initiation and progression of periodontal lesions, and in samples with clinical resolution. Age effects and relationship of AMF to the dominant members of the oral microbiome were also evaluated. AMF could be stratified into 4 groups with high (n = 22), intermediate (n = 29), low (n = 18) and very low (n = 45) expression in healthy adult tissues. A subset of AMF were altered in healthy young, adolescent and aged samples compared with adults (e.g., APP, CCL28, DEFB113, DEFB126, FLG2, PRH1) and were affected across multiple age groups. With disease, a greater number of the AMF genes were affected in the adult and aged samples with skewing toward decreased expression, for example WDC12, PGLYRP3, FLG2, DEFB128, and DEF4A/B, with multiple age groups. Few of the AMF genes showed a >2-fold increase with disease in any age group. Selected AMF exhibited significant positive correlations across the array of AMF that varied in health and disease. In contrast, a rather limited number of the AMF significantly correlated with members of the microbiome; most prominent in healthy samples. These correlated microbes were different in younger and older samples and differed in health, disease and resolution samples. The findings supported effects of age on the expression of AMF genes in healthy gingival tissues showing a relationship to members of the oral microbiome. Furthermore, a dynamic expression of AMF genes was related to the disease process and showed similarities across the age groups, except for low/very low expressed genes that were unaffected in young samples. Targeted assessment of AMF members from this large array may provide insight into differences in disease risk and biomolecules that provide some discernment of early transition to disease.

Dataset Information

Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.

Publications

Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.

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