Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function

TL;DR

This study shows that defects in tooth enamel formation can weaken the gum barrier, increasing susceptibility to infection and inflammation.

Contribution

This is the first study to investigate how defective ameloblast differentiation and enamel matrix formation affect junctional epithelium structure and function.

Findings

Mice with defective enamel matrix proteins show altered junctional epithelium morphology and reduced adhesion.

Mutant mice exhibit increased permeability and compromised barrier function in the junctional epithelium.

Reduced β-catenin and Ki67 in mutants suggest impaired epithelial regeneration and mitotic activity.

Abstract

The gingival sulcus, a natural pocket around teeth, is prone to trapping food particles and bacteria, often leading to infection and inflammation that damage the epithelial barrier and the underlying periodontal ligament, cementum, and alveolar bone. If left untreated, this infection can progress to periodontitis, a chronic disease affecting 20–50% of the global population and costing the U.S. USD 154.06 billion in treatment in 2018. The junctional epithelium lines the gingival sulcus, serving as a protective barrier and anchoring the gingiva to the enamel to seal and prevent infiltration by food and pathogens. The junctional epithelium originates from the reduced enamel epithelium, comprising the late developmental stage of ameloblasts, cells that form the enamel tissue. This study investigates whether defective ameloblast differentiation and enamel matrix formation impair junctional epithelium structure and weaken its protective function. In mouse models lacking the key enamel matrix protein amelogenin (Amelx−/−) or enamel matrix proteinase kallikrein-related peptidase 4 (KLK4) (Klk4−/−), we observed altered junctional epithelial cell morphology, reduced matrix–cell and cell–cell adhesion, and increased Dextran-GFP penetration, indicating a more permeable barrier and compromised seal. Reduced β-catenin and Ki67 at the junctional epithelium’s base in mutants suggest impaired epithelial regenerative capacity. These findings imply the critical roles of ameloblasts and enamel matrix in the development of healthy gums.

The junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No prior studies have investigated whether defective ameloblast differentiation or enamel matrix formation affects junctional epithelium anatomy or function. Here, we examined the junctional epithelium in mice exhibiting amelogenesis imperfecta due to loss-of-function mutations in the major enamel matrix protein amelogenin (Amelx−/−) or the critical enamel matrix protease KLK4 (Klk4−/−). Histological analyses demonstrated altered morphology and cell layer thickness of the junctional epithelium in Amelx−/− and Klk4−/− mice as compared to wt. Immunohistochemistry revealed reduced ODAM, laminin 5, and integrin α6, all of which are critical for the adhesion of the junctional epithelium to the enamel in Amelx−/− and Klk4−/− mice. Furthermore, we observed altered cell–cell adhesion and increased permeability of Dextran-GFP through the mutants’ junctional epithelium, indicating defective barrier function. Reduced β-catenin and Ki67 at the base of the junctional epithelium in mutants suggest impaired mitotic activity and reduced capacity to replenish continuously desquamated epithelium. These findings highlight the essential role of normal amelogenesis in maintaining junctional epithelium homeostasis.

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