Structure and Biology of the Cementum as a Function of Age and Disease

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PROJECT SUMMARY Aging is an inevitable progressive series of events that effect all living organisms. Structural and compositional changes that occur to mineralized tissues during aging can deteriorate their function and regeneration. Cementum is a connective mineralized tissue that provides support, by attaching collagen fibrils from the periodontal ligament to the tooth, and function by absorbing mechanical loads during mastication. Periodontal disease is an infections chronic inflammatory condition that is highly prevalent in the older population and directly effects the biology and function of the cementum. However, the underlying functional properties of cementum with aging are not fully elucidated. The hypothesis is that modifications to the composition and structure will degrade the functionality and regeneration of the cementum with aging, and potentially enhance the progression of periodontal disease. The proposed aims consist of identifying the biochemical, structural, and mechanical features of the aging cementum (Aim 1), defining the state of periodontally involved cementum as a function of age (Aim 2) and delineating in vivo biochemical, physico-mechanical and molecular mechanisms in cementum to unveil the impact of aging and periodontal disease using ligature-induced periodontitis model (Aim 3). The aims of this proposal integrate important events (aging and disease) of living organisms, in particular their effects in oral health. This proposal is elaborated based on the candidate’s biomaterials and matrix biology experience and plans to support the achievement of specialized skills in cementum biology, structural and protein analysis, and in vivo animal models to pursue an independent research career. An experienced advisory team was assembled to provide expertise in tooth ultrastructure and biomechanics (Dr. Ana Bedran-Russo, primary mentor), protein analysis and murine periodontitis model (Dr. Afsar Naqvi, co-mentor), immunohistochemistry and regeneration (Dr. Xianghong Luan, co-mentor), morphometrics (Dr. Jeffrey Toth, collaborator), clinical periodontics support (Dr. Vrisiis Kofina) and ECM proteomics and bioinformatics (Dr. Alexandra Naba, consultant). The career development plan is structured to advance in the gaps of scientific and professional skills related to the aims of the proposal. It is composed of didactic courses, workshops and activities that combined with an organized mentoring dynamic will allow the candidate to achieve specific milestones to obtain an independent faculty position. The completion of the proposed aims will reveal uncharted areas of the structure, biology and biomechanics of the cementum as a function of age and disease, and the impact of these processes on cementum regeneration. Potential molecular mechanisms of cementum aging elucidated in this proposal could build a foundation for understanding mineral-to-matrix interactions and their probable roles in the functionality and regeneration of mineralized tissues.