Understanding And Enhancing Regenerative Capacity Of The Junctional Epithelium

Periodontitis is one of the most prevalent chronic inflammatory diseases worldwide leading to progressive damage to the supporting tissues of the teeth (known as the periodontium). The oral epithelium acts as a barrier preventing invasion of microbes in the mouth. A particularly sensitive area is the epithelium that sits between the oral epithelium and the tooth, known as the junctional epithelium which protects the tooth-supporting structures from the oral environment. This epithelium forms a tight connection to the enamel and cementum of the tooth via an inner basement membrane rich in collagens and laminins and rapidly renews itself controlled by a stem cell niche. If the junctional epithelium becomes detached from the tooth surface an epithelial pocket is created. The loss of attachment disrupts the protective effects of the junctional epithelium, leading to further destruction of the periodontal tissues, ultimately resulting in loss of bone, and tooth loss. We hypothesis that if junctional epithelium could be stimulated in periodontal disease, the regression of the epithelium could be reversed, providing a novel regenerative therapy for periodontal disease. In this application we focus on the junctional epithelium to understand this unique and essential structure. We aim to follow the development of the junctional epithelium and establishment of its stem cells niche. We will then investigate how this tissue is impacted in case of disease and detachment from the tooth. Finally, we will assess how attachment and the stem cell niche can be maintained or reconstructed. Aim 1: To map the signals and cell populations that form and maintain the junctional epithelium Aim 2: To characterise the mechanisms underlying loss of attachment Aim 3: To rescue the regression of the junctional epithelium in periodontal disease In this proposal we focus on the mouse. Mouse molars are very similar to human molars and are also supported by a junctional epithelium that expresses many of the same genes as in humans. Genetically modified mouse models allow us to target specific tissues, while periodontitis models can be generated to explore how the tissue reacts to a disease state. In addition to knowledge about prevention of periodontitis, knowledge of how to form a functional junctional epithelium will also help to improve the interaction between the oral epithelium and dental implants. The proposal is a collaboration between a researcher with a background in tooth development and repair, and a clinician specialising in the periodontal tissues, bringing together their expertise to answer an important question which impacts a large proportion of the population.