Comparative Analysis of Gene Expression Patterns for Oral Epithelial Cell Functions in Periodontitis

Abstract

The structure and function of epithelial cells are critical for the construction and maintenance of intact epithelial surfaces throughout the body. Beyond the mechanical barrier functions, epithelial cells have been identified as active participants in providing warning signals to the host immune and inflammatory cells and in communicating various detailed information on the noxious challenge to help drive specificity in the characteristics of the host response related to health or pathologic inflammation. Rhesus monkeys were used in these studies to evaluate the gingival transcriptome for naturally occurring disease samples (GeneChip® Rhesus Macaque Genome Array) or for ligature-induced disease (GeneChip® Rhesus Gene 1.0 ST Array) to explore up to 452 annotated genes related to epithelial cell structure and functions. Animals were distributed by age into four groups: ≤ 3 years (young), 3–7 years (adolescent), 12–16 years (adult), and 18–23 years (aged). For naturally occurring disease, adult and aged periodontitis animals were used, which comprised 34 animals (14 females and 20 males). Groups of nine animals in similar age groups were included in a ligature-induced periodontitis experiment. A buccal gingival sample from either healthy or periodontitis-affected tissues were collected, and microarray analysis performed. The overall results of this investigation suggested a substantial alteration in epithelial cell functions that occurs rapidly with disease initiation. Many of these changes were prolonged throughout disease progression and generally reflect a disruption of normal cellular functions that would presage the resulting tissue destruction and clinical disease measures. Finally, clinical resolution may not signify biological resolution and represent a continued risk for disease that may require considerations for additional biologically specific interventions to best manage further disease.

Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis

“…Consequently, they are essential for coordinating gene expression and directing various biological responses, and their dysregulation is strongly associated with human diseases [69]. Despite the significance of TFs in disease, periodontal research has focused primarily on identifying differentially expressed genes and deducing their functions through associated signaling pathways [16][17][18][19][20][21][22][23][24][25][70][71][72][73][74]. Moreover, changes in TFs expression are not always accompanied by alterations in functional activity.…”

“…Different omics technologies have benefited personalized medicine by enabling simultaneous and in-depth whole genome molecular analysis in response to environmental cues at any given time [14,15]. In particular, in the numerous in vitro and in vivo studies that have contributed to a partial understanding of the molecular mechanisms underlying the pathogenesis of periodontitis, the most frequently utilized technique has been the transcriptome microarray [16][17][18][19][20][21][22][23][24][25]. In this study, we employed high-throughput RNA sequencing (RNA-Seq), the standard approach for understanding the changes in RNA levels underlying cellular responses induced by environmental perturbations [26].…”

Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine

“…Further, when comparing the group that underwent preventive Metformin administration versus the group on water prior to disease induction, our results showed that in the Metformin group, the epithelial cells upregulated Krt76 and Krt6a (genes important for epithelial immune reaction and differentiation [ 50 ]), Gas5 (a gene important for glucocorticoid receptor control which modulates insulin resistance [ 51 ]), and Fxyd3 (a regulator of Na + /K + ATPases, maintaining osmotic equilibrium and membrane potential in epithelial cells [ 52 ]) (Additional file 12 : Fig. S5B, Additional file 16 : Table S1, Additional file 4 ).…”

Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer’s Disease (AD)

“…In a particular study, it was found that CALD1 expression was significantly increased in the brains of people with AD compared to those without the condition and that CALD1 may be involved in the production of amyloid beta, a protein that is believed to be a key contributor to the development of AD [ 17 , 18 ]. Some research has suggested that CALD1 may be involved in the development of periodontitis, a type of gum disease characterised by inflammation and loss of the tissue and bone that support the teeth [ 19 , 20 ]. It was found that CALD1 expression was significantly increased in the gingiva of people with periodontitis compared to those without the condition and that CALD1 may be involved in the immune response to periodontitis.…”