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

Abstract

Aim Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since aging 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. Materials and Methods 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. Results 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. Conclusion A pro-osteoclastogenic gingival transcriptome is associated with periodontitis irrespective of age; however; a greater bone-destructive molecular environment is associated with aging in healthy tissues.

Host‐microbe interactions: Profiles in the transcriptome, the proteome, and the metabolome

“…The main methods currently used in transcriptomic studies include RNA sequencing and microarray analyses 3,[8][9][10][11][12][13][14][15][16][17][18][19] (Table 1). RNA sequencing effectively demonstrates periodontitis-related gene expression.…”

“…Specifically, genes related to osteoclast function exhibit enhanced expression (secreted phosphoprotein 1, toll like-receptor 4, matrix metallopeptidase 8, and transcription factor EC), and those related to osteoblast activity are impaired (protein phosphatase 4 regulatory subunit 3C and SMAD family member 5). 14 The effects of smoking on the periodontium have been widely investigated in clinical and animal studies. [21][22][23] Transcriptomic studies have revealed that smoking mediates epigenetic modifications on the extracellular matrix organization of the periodontium, which subsequently enhances disease progression and accelerates tissue destruction.…”

Oral Manifestation on Systemic Lupus Erythematosus Patients

“…Resulting DNA damage, lipid peroxidation, protein, other important enzyme oxidation and stimulation in the release of proinflammatory cytokines by monocytes and macrophages. Inflammatory chronic induce collagen breakdown, RANKL, osteoclast stimulation until alveolar bone resorption (Pandruvada, 2016).…”

“…In SLE patients the occurrence of hyperactivity of dendritic cells and hypoactivity of T-cell reg. Hypoactivity of Treg cells causes directly killing itself and vulnerable to infection (Pandruvada, 2016).…”

Age and Periodontal Health—Immunological View

“…Alterations in gene expression in periodontitis particularly in aged animals were skewed towards creating an environment with substantial osteoclastogenic potential consistent with the bone resorption in periodontitis (Supplemental Figure 2). These data indicated that local bone resorptive processes are up-regulated under the condition of aging creating a tissue destructive environment [134]. More recently, we evaluated the potential interaction between human antibody responses to P. gingivalis and activation of osteoclasts (OC) as an entry point into more critical definition of how these antibodies might function in health and disease.…”