Quantitative Mechanical/Chemical Imaging of Bone from Dmp1 Null Mice

Abstract

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein which plays an important role in mineralized tissue formation. Dmp1 null adult mice are ricketic and osteomalacic and are a model for hypophosphatemic rickets [1]. Mutation in humans results is Autosomal Recessive Hypophosphatic Rickets [1]. The degree of bone mineralization significantly contributes to bone tissue mechanical properties, but precise relationships and interactions between chemical and mechanical variables are unknown. The objective of this study was to relate the differences in chemical properties in the Dmp1 wildtype (WT) and null (KO) mouse femoral cortical bone to their mechanical properties by using FTIR imaging and Scanning Acoustic Microscopy (SAM). Interactive mechanical (elastic modulus) and chemical images (i.e., mineral/matrix ratios) were generated from the same region of bone at a lateral resolution of ˜10 um. Mechanical analysis showed that elastic modulus, 75 percentile around 7.1 GPa, was ˜60% less in Dmp1 KO than that in WT, in which elastic modulus was 75 percentile around 15.2 GPa. The mineral-to-matrix ratios in Dmp1KO (4.96±1.63) were ˜2 times lower than that in Dmp1 WT (8.65±1.14). The mineral crystallinity and collagen crosslink ratios were not significantly different between KO and WT. Conclusions: The results relate the bone elastic modulus changes in Dmp1WT and KO mice with chemical changes within a specific bone site. These measurements provide a new tool for describing the variability of bone chemical and mechanical properties.