Dentin-pulp dynamics of aging teeth

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PROJECT SUMMARY/ABSTRACT The introduction of new strategies harnessing the regenerative capacity of the dentin-pulp complex may make it possible for humans to retain their natural teeth throughout their lifespan. Research has demonstrated that dental pulp stem cells maintain extraordinary characteristics that can provide clinical options for dental care and restoration. However, it remains unknown whether older patients are also able to benefit from these tech- nologies. The long-term goal of this project is to gain an understanding of how teeth change throughout adult- hood in order to develop treatments that can preserve or enhance tooth health and permit retention throughout the lifespan. Our objective is to analyze the dentin-pulp interface in young and old rodent molars to qualitatively determine how the regenerative capacity of the dentin-pulp complex changes with age. Our central hypothesis is that age-related changes to the DP mesenchyme, vasculature, and innervation alter the secretion and avail- ability of bioactive proteins in dentin (BPiD) and that pulpal senescence, in combination with reduced access to BPiD, reduces tooth vitality with age. The rationale for this project is that a detailed scientific framework of tooth aging and regeneration is likely to uncover molecular candidates for vital pulp therapies. The central hy- pothesis will be tested with the following specific aims: 1) Identify secreted bioactive proteins in dentin that change with age; and 2) Analyze age-dependent changes in teeth. Under the first aim, molars from young and old rats will be extracted, divided into root and crown portions, and milled for subsequent proteomic analyses of the dentin composition. ELISA and/or immunofluorescence will verify location and abundance in order to iden- tify secreted proteins of interest that could regulate neurovascular responses during injury and/or regeneration. For the second aim, mouse molar dentin in 3- and 20-month mice will be surgically damaged and analyzed at varying time points to assess: a) elasticity and hardness using nanoindentation assays; b) mineralized volume and density determined by microcomputed tomography (micro-CT); and c) dental pulp neurovascular injury responses based on confocal imaging. The research proposed in this application is innovative because it pro- vides a comprehensive view of how teeth age using several techniques applied to preclinical murine models from young and elderly stages. The proposed research is significant because it is expected to identify vital pulp therapy and regenerative endodontics candidates for continued research and future clinical trials with patients in different stages of life. Ultimately, such knowledge has the potential to offer new dental treatments to help patients maintain their dental health and retain their natural teeth into old age.