Quantitative Multiscale Characterisation of Dental Enamel Pathologies associated with Hypomature Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous condition that compromises dental enamel formation. Among the key proteases implicated in AI are matrix metalloproteinase-20 (MMP20) and kallikrein-related peptidase-4 (KLK4), which function sequentially during enamel development as extracellular matrix proteinases. Mutations in these two proteins have been associated with the development of the hypomature subtype of AI due to the compromised function to effectively degrade and remove enamel proteins during enamel formation and mineralisation. As a result, the produced enamel becomes hypomineralized.
This study included a comprehensive physical characterization of 10 affected MMP20 and KLK4 samples. Matching controls for all the tooth types were included. MMP20 mutations studied were one dental sample with a missense mutation at c.625G>C, and four with a homozygous frameshift mutation at c.954-2A>T. All KLK4 samples had a homozygous frameshift mutation at c.632delT. All samples were subjected to microcomputed tomography to assess mineral density, SXRD scanning to analyse texture distribution and orientation and SEM to link microstructural disruptions to the mineral and crystallographic data.
Our findings indicate that MMP20 was more severely affected at all levels of analysis, with mineral density, microstructure, and texture showing greater disruption as a result of the mutation. In contrast, KLK4 largely preserved a high degree of organisation and mineral density, particularly at the enamel surface.
MMP20 samples have shown more pathogenic effect on the enamel hierarchical structure than KLK4, despite KLK4 teeth presenting more discolourations. We conclude that MMP20 is more critical for correct enamel formation across multiple length scales and therefore dentists can plan treatment for their KLK4 diagnosed patients to be more preservative.