DSPP effects on in vivo bone mineralization

Abstract

Dentin sialophosphoprotein has been implicated in the mineralization process based on the defective dentin formation in Dspp null mice (Dspp-/-). Dspp is expressed at low levels in bone and Dspp-/-femurs assessed by quantitative micro-computed tomography (microCT) and Fourier transform infrared spectroscopic imaging (FTIRI) exhibit some mineral and matrix property differences from wildtype femurs in both developing and mature mice. Compared to wildtype, Dspp-/-mice initially (5 weeks) and at 7 months had significantly higher trabecular bone volume fractions and lower trabecular separation, while at 9 months, bone volume fraction and trabecular number were lower. Cortical bone mineral density, area, and moments of inertia in Dspp-/-were reduced at 9 months. By FTIRI, Dspp-/-animals initially (5 months) contained more stoichiometric bone apatite with higher crystallinity (crystal size/perfection) and lower carbonate substitution. This difference progressively reversed with age (significantly decreased crystallinity and increased acid phosphate content in Dspp-/-cortical bone by 9 months of age). Mineral density as determined in 3D micro-CT and mineral-to-matrix ratios as determined by 2D FTIRI in individual cortical and trabecular bones were correlated (r 2 =0.6, p<0.04). From the matrix analysis, the collagen maturity of both cortical and trabecular bone was greater in Dspp-/-than controls at 5 weeks; by 9 months this difference in crosslinking pattern did not exist. Variations in mineral and matrix properties observed at different ages are attributable, in part, to the ability of the Dspp gene products to regulate both initial mineralization and remodeling, implying an effect of Dspp on bone turnover.

Expression of Dentin Sialophosphoprotein in Non-mineralized Tissues

“…This difference in the DSPP expression levels between these non-mineralized tissues and bone was further confirmed by other approaches, such as β-galactosidase expression assays, in the Dspp knockout mice. A previous study has shown phenotypic changes in the long bone in the Dspp knockout mice (Verdelis et al 2008). The significantly higher level of DSPP expression in the salivary glands, cartilage, liver, and kidney suggests that DSPP might play important roles in these soft tissues.…”

“…On the other hand, DSP, a glycoprotein with little or no phosphate, was discovered in 1981 (Butler et al 1981). The importance of DSPP in biomineralization has been illustrated in human and mouse genetic studies that revealed the association of Dspp mutations or ablations with mineralization defects in the dentin and bone (Sreenath et al 2003;Verdelis et al 2008;Xiao et al 2001;Zhang X et al 2001).…”

The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling

“…At 5 weeks of age, these mice displayed accelerated mineralisation, while at 9 months of age significant changes in bone structural properties were observed. This therefore suggests that DSPP has roles not only in the initial mineralisation of bone but also in the remodelling of the skeleton and therefore on bone turnover (Verdelis et al 2008).…”

“…Although originally thought to be exclusively expressed by dentin, DSPP is also expressed in bone, cementum and in non-mineralising tissues including the lung and kidney (Qin et al 2002, Baba et al 2004, Alvares et al 2006, Ogbureke & Fisher 2007, Verdelis et al 2008.…”

“…Analysis of the Dspp knockout mouse reveals defects in dentin mineralisation (Sreenath et al 2003), as well as bone hypomineralisation (Verdelis et al 2008). In humans, a mutation in the DSPP gene results in dentinogenesis imperfecta, characterised by dentin hypomineralisation and significant tooth decay (Kim et al 2005).…”