Overexpression of DMP1 accelerates mineralization and alters cortical bone biomechanical properties in vivo

Dentin matrix protein-1 (DMP1) is a key regulator of biomineralization. Here, we examine changes in structural, geometric, and material properties of cortical bone in a transgenic mouse model overexpressing DMP1. Micro-computed tomography and three-point bending were performed on 90 femora of wild type and transgenic mice at 1, 2, 4, and 6 months. Fourier transform infrared imaging was performed at 2 months. We found that the transgenic femurs were longer (p<0.01p<0.01), more robust in cross-section (p<0.05p<0.05), stronger (p<0.05p<0.05), but had less post-yield strain and displacement (p<0.01p<0.01), and higher tissue mineral density (p<0.01p<0.01) than the wild type femurs at 1 and 2 months. At 2 months, the transgenic femurs also had a higher mineral-to-matrix ratio (p<0.05p<0.05) and lower carbonate substitution (p<0.05p<0.05) compared to wild type femurs. These findings indicate that increased mineralization caused by overexpressing DMP1 led to increased structural cortical bone properties associated with decreased ductility during the early post-natal period.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (178 K)Download as PowerPoint slideHighlights► DMP1, a regulator of mineralization, was studied in post-natal transgenic mice. ►μμ-CT, 3-pt bending, and FTIRI showed differences at 1 and 2 months, but not at 4 or 6 months. ► Transgenic mice had early post-natal increases in structural properties and material density. ► Transgenic mice had early accelerated mineralization with decreased ductility.