Gingival tissue samples from periodontitis patients demonstrate epithelial–mesenchymal transition phenotype

Abstract

Objective: To determine the expression of key epithelial-mesenchymal transition (EMT) markers in gingival tissue samples collected from patients with periodontitis.Background: Epithelial-mesenchymal transition is a process responsible for shifting epithelial-phenotype to mesenchymal-phenotype leading to loss of epithelial-barrier function. Thus, EMT could be involved as a pathogenic mechanism in periodontitis as both conditions share common promoters and signalling pathways.Materials and Methods: Gingival tissue samples were collected from patients with periodontitis (case) and healthy periodontium (control). Periodontal parameters including bleeding on probing, probing pocket depth (PPD), and clinical attachment loss were recorded. Paraffinized tissue samples were processed and immunohistochemically stained to determine the expression of key EMT markers which included E-cadherin, β-catenin, Snail1 and vimentin. Results:The majority of cases (n = 65, 72.2%) were diagnosed with periodontitis stage 3 or 4, grade b or c vs 25 (27.8%) subjects with intact healthy periodontium. Discontinuity of epithelium was detected in up to 80.9% of periodontitis cases associated with reduced number of epithelial layers as compared to controls. Immunohistochemical expression of epithelial markers (E-cadherin and β-catenin)was significantly downregulated in periodontitis patients as compared with controls. Periodontitis cases exhibited significant upregulation of Snail1 expression. Furthermore, cytoplasmic vimentin (66.2%) and nuclear β-catenin (27.7%) were solely expressed in periodontally diseased tissues compared with control. Epithelial markers, E-cadherin and β-catenin, were significantly negatively correlated with increasing PPD, while vimentin showed positive correlation with this parameter. Conclusion:There were marked downregulation of epithelial molecules and upregulation of mesenchymal markers in gingival tissues derived from periodontitis patients, suggesting expression of the EMT phenotype in the pathological epithelial lining of periodontal pockets.

Ability of gingival crevicular fluid volume, E‐cadherin, and total antioxidant capacity levels for predicting outcomes of nonsurgical periodontal therapy for periodontitis patients

“…Consistent with this observation, the level of soluble E‐cadherin in salivary samples of periodontitis patients was found to be significantly higher than in healthy controls 21,22 . Furthermore, immunohistochemical analysis of periodontally diseased tissue samples demonstrated reduced E‐cadherin levels 16 …”

“…Recent immunohistochemical studies have indicated that the expression of E‐cadherin is significantly reduced in biopsies collected from periodontally‐diseased sites 16 . Previous work has also found a significant increase in the concentration of β‐catenin, a key molecule responsible for connecting E‐cadherin to the cytoskeleton, in GCF of periodontitis patients which indirectly suggesting the release of E‐cadherin 38 .…”

“…25,26 Increasing oxidative stress is a shared risk factor between periodontitis 12 and EMT process 27 which recently linked to pathogenesis of periodontitis. 16 Consistently, the level of soluble E-cadherin has been shown to increase significantly in oral fluids from periodontally diseased subjects, compared with healthy controls, 22 as a consequence of periodontitis-associated destructive events. Consequently, we hypothesized that mechanical eradication of bacterial load from subgingival area would restore redox potential to normal levels thereby restoring soluble E-cadherin levels in GCF.…”

“…21,22 Furthermore, immunohistochemical analysis of periodontally diseased tissue samples demonstrated reduced E-cadherin levels. 16 Successful periodontal therapy outcomes are the goal of appropriately targeted treatment plans. Current guidelines for treating periodontitis are directed toward controlling biofilms and other risk factors followed by subgingival instrumentation, while surgical procedures are generally only applied following multiple courses of nonsurgical therapy in a compliant patient.…”

“…Persistent exposure to inflammatory cytokines and oxidative stress are considered as risk factors responsible for compromising the epithelial phenotype resulting in the loss of epithelial layer coherence and barrier function. Clinically this is characterized by microulceration of the epithelial pocket lining 16,17 leading to bleeding even following only relatively gentle probing. Destruction of AJs and the release of the unbounded E‐cadherin due to proteolytic cleavage is evident in a range of inflammatory diseases 18–20 .…”