Unraveling dentin and enamel roles on the development and progression of wedge-shaped noncarious cervical lesions - PROJECT SUMMARY/ABSTRACT Noncarious cervical lesions (NCCLs) are a common dental condition that can result in significant loss of tooth structure and pain, affecting the individual throughout their lifetime. Available intervention options for this condition are limited and not effective long-term. This condition has high prevalence among adults (up to 85% in specific populations), however there is scarce information concerning mechanisms leading to the condition and its progression, especially for wedge-shaped NCCLs. The on-set of these lesions, which can affect different teeth in the individual cannot be explained based on current evidence. There is a significant gap in the understanding of mechanisms behind dentin breakdown during the establishment of wedge-shaped lesions, which may be linked to changes in the dentin organic matrix composition and morphology. Our preliminary data has shown compositional differences of NCCL-affected teeth when compared to sound teeth, indicating that there is a critical need to evaluate the specific roles that enamel and dentin may play in the development and progression of this prevalent condition. The goal of this R03 is to investigate the individual relative contributions leading to tooth breakdown, characterized by loss of mineral and organic components, largely affecting dentin within the cementoenamel junction. To achieve this goal we will investigate compositional, morphological, and histological changes in the affected dentin and enamel (aim 1); and the relationships between those and the biomechanical properties of NCCL-affected dental tissues that could impair the protective mechanisms of the tooth. Dentin and enamel biomechanical properties will be characterized at the nanoscale and relationships will be investigated between key components of the dentin extracellular matrix, including biodegradative mechanisms and the nanomechanical properties of the wedge-shaped NCCL-affected (bounding) tissue (aim 2). Our approach is innovative considering previously unknown factors related to this prevalent condition and providing data for future comprehensive funding mechanisms. Furthermore, these findings will be the key to our long-term translational goal, which is the establishment of targeted successful therapeutic approaches for the prevention and decrease in prevalence of this condition.