A Review of a Breakdown in the Barrier: Tight Junction Dysfunction in Dental Diseases

Abstract

The tight junction (TJ), a type of cell-cell junction, regulates the permeability of solutes across epithelial and endothelial cellular sheets and is believed to maintain cell polarity. However, recent studies have provided conflicting views on the roles of TJs in epithelial polarity. Membrane proteins, including occludin, claudin, and the junction adhesion molecule, have been identified as TJ components. TJs are predominantly found at the stratum granulosum and stratum corneum. Although it remains unclear whether the disruption of TJs is the cause or consequence of certain dental diseases, evidence suggests that TJ dysfunction may be a crucial factor in gingival epithelial barrier impairment and the progression of oral diseases. Bacterial infection is among the most specific factors we found that may contribute to the breakdown of the epithelial barrier formed by TJs in dental diseases. Bacteria and their products may weaken the epithelial barrier by directly destroying intercellular junctions or altering the expression of junctional proteins. Additionally, they may induce the production of inflammatory cytokines, which could lead to the downregulation of TJ proteins and, consequently, impair the epithelial barrier. This review introduces a novel perspective by exploring, for the first time, the role of TJs dysfunction in the breakdown of the oral epithelial barrier and its potential link to the progression of dental diseases such as gingivitis, periodontitis, Sjӧgren syndrome, and oral squamous cell carcinoma.

Keywords: Sjӧgren syndrome; epithelial barrier; gingival inflammation; oral squamous cell carcinoma; periodontitis.

Figure 1

Cell-cell junctions and structure of tight junctions in epithelium. (A) Some types of cell-cell junctions. (B) Structure and proteins of tight junctions between epithelial cells. Claudin forms the tight junction strand that interacts with ZO. No sequence similarity exists between claudin and occludin. ZO proteins are tight junction scaffold proteins that link actin filaments to tight junctions. This figure is the authors’ graphical work drawn using Inkscape 1.3.2.

Figure 2

Structure of periodontium and demonstration of tight junction location in oral epithelium. (A) Anatomy and histology of the gingival unit. (B) Localization of tight junctions in gingival stratified squamous epithelium. This figure is the authors’ graphical work drawn using Inkscape 1.3.2.

Figure 3

An overview of gingivitis and periodontitis. The process begins with the accumulation of dental plaque (A), a complex biofilm formed by the colonization of bacteria enclosed by a protective matrix. (B) If this biofilm is not disrupted and continues to accumulate, plaque bacteria produce toxins that penetrate the gingival tissues. The host responds to this bacterial infection with the classical innate immune response, where pathogens trigger leukocytes to release proinflammatory mediators, such as cytokines and chemokines. This cascade of reactions activates adaptive immunity, involving specific T and B lymphocytes. Neutrophils and macrophages, activated by these lymphocytes, release proinflammatory cytokines that increase vascular permeability. These immune cells migrate to the gingival tissue through the bloodstream, causing the gingival tissues to become red, swollen, tender, and more prone to bleeding. (C and D) If untreated, gingivitis can lead to early periodontitis, where the gingiva pulls away from teeth, forming pockets and causing attachment and bone loss. This figure is the authors’ graphical work drawn using Inkscape 1.3.2.

Figure 4

Clinical case: Gingivitis. (A) Frontal view. (B) Right buccal view. (C) Left buccal view. This figure is from Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy in Vietnam. The patient provided consent to publish the images.

Figure 5

Clinical case: Periodontitis. (A) Occlusal view of the upper arch. (B) Occlusal view of the lower arch. (C) Right buccal view. (D) Frontal view. (E) Left buccal view. This figure is from Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy in Vietnam. The patient provided consent to publish the images.