Effects of Osteogenesis Imperfecta on Dental Tissue Volumes in Mice

Abstract

Osteogenesis imperfecta (OI), commonly known as brittle bone disease, is associated with lifelong dental problems, including increased dental fractures, discolored teeth, and malocclusion. OI is a disorder of the type I collagen protein. Insufficient amounts or misshapen forms of this protein lead to disruptions in the microstructure of bone and teeth tissues. Dentin, the hard tissue which comprises the bulk of the tooth and absorbs shock forces during chewing, develops on a type I collagen matrix. Thus, collagen abnormalities in OI lead to disorganized and less stable dentin. Further, teeth in people with OI frequently exhibit dentin hypertrophy, where increased amounts of dentin are deposited at the interior of the tooth, shortly after dental eruption. Enamel, unlike dentin, develops on a matrix of non-collagenous proteins, and is thought to develop normally in OI. However, abnormalities in the underlying dentin in OI can lead to enamel fractures. Finally, the teeth in people with OI have often been noted to be smaller than those of people without OI. Because dental development occurs early in life, there is a lack of data surrounding the developmental processes and associated issues in dental development of children with OI. Mice are commonly used models for dental development, yet, this process has not yet been studied in mice. The objective of this study is to compare dental tissue volumes of teeth from mice with OI (oim) and wild type mice (wt) at different developmental stages to determine the degree of volume and gross dental size differences during late growth stages. Three-dimensional models of upper and lower first molars and incisors were created from microCT scans from oim and wt mice. Scans were taken at weaning age (four weeks after birth; "W4") and young adulthood (sixteen weeks after birth; "W16"). Dental tissue volumes were measured using 3D Slicer and normalized to mandibular centroid size. Mann-Whitney U tests were used to compare tissue volumes between genotypes and age groups. At W4 and W16, oim mice had significantly lower dentin volumes and total tooth volumes for upper incisors than wt mice (p < 0.05), with no significant difference between groups for other tooth types at either timepoint. At W16, total tooth volume was significantly lower in oim mice for molars before adjusting for mandible size (p < 0.05). For both oim and wt groups, W16 mice had significantly greater dentin, enamel, and total tissue volumes for lower and upper incisors compared to W4 mice (p < 0.05), as well as greater dentin volumes for lower molars (p < 0.05). These results demonstrate that the trend of smaller teeth in humans with OI also holds for the oim mouse. These differences are present at both the juvenile and young adult life stages. This affirms the oim mouse as a possible model for dental development in humans with OI. Further studies are needed to determine the developmental program of these volume differences at earlier growth stages.