Wednesday, March 12, 2025
3/12/2025
PROJECT SUMMARY/ABSTRACT Molar-Incisor Hypomineralization (MIH) is a highly prevalent in children all around the globe affecting their primary and permanent teeth. The affected enamel has chalky to yellow lesions that are demarcated and less mineralized causing increased caries susceptibility, enamel breakout, esthetic concerns and sensitive teeth. While the treatment and management of these lesions are challenging, the pathophysiology of MIH is not known, hampering the development of a precise, targeted therapy. A striking feature of MIH is the demarcation of defects, such that affected and unaffected enamel are located adjacently, with abrupt changes in mineral density. This feature is in stark contrast to fluorosis which is characterized by diffuse hypomineralization. Ameloblastin is one of the essential enamel proteins required for proper enamel formation. In the absence of ameloblastin enamel is hypoplastic, known as amelogenesis imperfecta. When ameloblastin is expressed too much, the enamel displays demarcated, hypomineralized lesions in mice. The pathoetiology of MIH is unknown. Exposure to environmental toxicants are currently discussed. The enamel of MIH teeth is characterized by an imbalance of enamel proteins and enzymes degrading the m atrix. The hypothesis of this research is that ameloblastin overexpression causes demarcated and hypomineralized lesions through enzymatic imbalance. The proposed Aims will define the pathways of demarcated enamel hypomineralization caused by Ambn overexpression and insufficient enzyme. In SA1 we will determine if demarcated, hypomineralized lesions are caused by insufficient enzyme relative to ameloblastin overexpression. In SA2, we will determine the transcriptome and transcriptional regulation of Ambn and overexpressed Ambn in ameloblasts using cultured primary enamel organ epithelium, termed ‘ameloblastoids’. In SA3, findings from the mouse model will be translated into a minimally invasive MIH treatment protocol addressing conditioning and infiltrating the porous, hypomineralized enamel. Ultimately, this project will bridge the gap in MIH treatment by translating basic and preclinical research into clinical research.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).