Mineral and Matrix Changes in Brtl/+Teeth Provide Insights into Mineralization Mechanisms

Abstract

The Brtl/+ mouse is a knock-in model for osteogenesis imperfecta type IV in which a Gly349Cys substitution was introduced into one COL1A1 allele. To gain insight into the changes in dentin structure and mineral composition in these transgenic mice, the objective of this study was to use microcomputed tomography (micro-CT), scanning electron microscopy (SEM), and Fourier transform infrared imaging (FTIRI) to analyze these structures at 2 and 6 months of age. Results, consistent with the dental phenotype in humans with type IV OI, showed decreased molar volume and reduced mineralized tissue volume in the teeth without changes in enamel properties. Increased acid phosphate content was noted at 2 and 6 months by FTIRI, and a trend towards altered collagen structure was noted at 2 but not 6 months in the Brtl/+ teeth. The increase in acid phosphate content suggests a delay in the mineralization process, most likely associated with the defect in the collagen structure. It appears that in the Brtl/+ teeth slow maturation of the mineralized structures allows correction of altered mineral content and acid phosphate distribution.

Bone mineral properties in growing Col1a2+/G610C mice, an animal model of osteogenesis imperfecta

“…The ratio is dependent on the environment around the carbonyl bonds in the peptide, and thus could be influenced by alterations in chain properties due to impaired triple-helix formation 35 , variations in d-spacing 36 or changes in collagen-noncollagenous protein interactions 33 . Our findings in Col1a2 +/G610C mice are consistent with those we observed in other OI mouse models, including Col1a2 oim/oim , Col1a1 Brtl/+ , fro/fro and the Pedf −/− mice 14,21,24,25,26,27,28,29,30,31,37 . Mineral-to-matrix ratio relates to bone mineral density as measured by dual photon absorptiometry and micro-CT 38 .…”

“…The amide I band, used as the denominator to assess the matrix contribution, is influenced by the environment in which the vibrating carbonyl-bonds sit, and hence any change in the association of noncollagenous proteins 33 can alter the position and intensity of this band. The collagen cross-link maturity, which is also elevated in other OI models 14, 32, 37 , may suggest disorganization and/or over-modification of abnormal mutant collagen fibrils. This parameter, although controversial 34 is widely used to study bone material properties and has been shown to correlate to enzymatic cross-links determined by HPLC 17 .…”

Studying Variations in Bone Composition at Nano-Scale Resolution: A Preliminary Report

“…Additionally, mapping drug effects, mapping changes in ligament and tendon insertions, as was done using standard FTIR imaging [25–27], and mapping changes in vascular tissues and teeth, also reported by standard FTIR imaging [28,29] will provide further opportunities for the optimization and utilization of this technique.…”

Guidelines for Micro–Computed Tomography Analysis of Rodent Dentoalveolar Tissues

“…Several inherited disorders affect dentinogenesis, including dentinogenesis imperfecta/dentin dysplasia, caused by mutations in dentin sialophosphoprotein (DSPP). Other mineralization disorders may affect dentin, including multiple forms of osteogenesis imperfecta (OI), hypophosphatasia (HPP), and genetic/congenital forms of hypophosphatemic rickets (48,(94)(95)(96)(97).…”