Dental Tissue Volumes in Mice with Osteogenesis Imperfecta

Abstract

Osteogenesis imperfecta (OI), commonly known as brittle bone disease, has long been known to cause significant dental problems that affect patients over the course of their lives, including increased dental fractures, discolored teeth, and malocclusion.At the molecular level, 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 matrix of type I collagen. Thus, collagen abnormalities in OI lead to less organized and less stable dentin.Further, the teeth in people with OI tend to exhibit dentin hypertrophy, in which increased amounts of dentin are deposited at the interior of the tooth. In humans with OI, dentin hypertrophy tends to develop shortly after the eruption of teeth into the oral cavity.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 frequently lead to enamel fractures. Finally, the teeth in people with OI have often been noted to be smaller than those of people without OI.Mice are the most commonly used animal model for dental development. However, differences in dental tissue volumes in OI have not yet been studied in mice.The objective of this study is to compare dental tissue volumes at different developmental stages in teeth from mice with and without OI. We hypothesize that both juvenile and young adult mice with OI will have smaller dental tissue volumes than mice without OI.To test this hypothesis, three‐dimensional models of teeth from OI mice (n = 10) and wild type mice (n = 10) were created from microCT scans taken at weaning age (week 4 after birth) and young adulthood (week 16 after birth). Dental tissue volumes were measured using 3D Slicer.Mann‐Whitney U tests showed that at week 16, mice with OI had significantly lower dental volumes compared to mice without OI for upper molars, lower molars, upper incisors, and lower incisors (p < 0.05). Additionally, at week 4, mice with OI had significantly smaller lower molars, upper incisors, and lower incisors (p < 0.05). There was no significant difference between the two groups in upper molar size among the week 4 mice.At week 16, the OI mice had significantly lower volumes of dentin compared to the mice without OI in the upper and lower molars (p < 0.05), but not in the upper or lower incisors. At week 4, the OI mice had significantly lower volumes of dentin compared to the mice without OI in the upper and lower incisors and lower molars (p <0.05), but not the upper molars.There were no significant differences between the two groups in enamel volume at either timepoint.These results demonstrate that mice with OI have smaller overall dental volumes compared to mice without OI, consistent with the human OI phenotype of smaller teeth.This research will provide important insights into the development of the dental phenotype in OI. The use of a mouse model to investigate dental tissue volumes represents a novel direction for OI research. Establishing the validity of the mouse model will allow future researchers to further characterize the effects of this disease on early dental development using methods, such as CT scans, that cannot be practically or ethically performed in young human patients.