PhD Studentship: A potential role for Epithelial Mesenchymal Trans differentiation (EMT) in the Pat

Periodontitis is a ubiquitous chronic inflammatory disease that destroys the supporting structures of teeth; the most common form is chronic periodontitis which if untreated results in the breakdown of soft tissues and bone, ultimately leading to tooth loss. Periodontal disease has also been associated with a range of systemic diseases including diabetes, cardiovascular disease and rheumatoid arthritis, with successful management of periodontitis associated with improved systemic disease outcomes. The disease is initiated by plaque bacteria present in a biofilm at and below the gingival margin, however the subsequent tissue damage that characterises this disease is the result of an aberrant and exaggerated host response within susceptible individuals (Matthews et al, 2006). The periodontal lesion is characterised by non-resolving chronic inflammation with frustrated healing and breakdown of the soft / hard tissue interface resulting in tissue loss.

Epithelial-mesenchyme Trans differentiation (EMT) has yet to be investigated for its potential role in the pathogenesis of periodontal disease. EMT is well characterised in other disease areas and results in frustrated healing and fibrosis both characteristic of the periodontal lesion. Induction of EMT within oral tissues may result in disruption of repair mechanisms and break down of the epithelial barrier allowing disease progression. Many of the previously reported risk factors which promote EMT at other disease sites are also relevant to periodontitis and include elevated levels of glucose, growth factors/cytokines, tobacco smoke and bacteria. This study aims to develop 2D and 3D oral keratinocyte in vitro EMT models using cell lines and primary cells. The induction of oral EMT by periodontitis risk factors in these systems will be assessed using a range of cellular, molecular and biochemical analyses. Potential inhibition of oral EMT will be determined following administration of a range of molecules and chemicals, such as antioxidants and vitamins. The pharmaceutical industry is also currently developing inhibitors for EMT which may have clinical application in periodontitis treatment.