Impaired mineral quality in dentin in X-linked hypophosphatemia.
X-linked hypophosphatemia (XLH) is a skeletal disorder arising from mutations in the PHEX gene, transmitted in most cases as an X-linked dominant trait. PHEX deficiency leads to renal phosphate wasting and hypophosphatemia, as well as impaired mineralization of bone and dentin, resulting in severe skeletal and dental complications. Dentin mineralization defects appear as characteristic, large interglobular spaces resulting from the lack of fusion of calculospherites in the circumpulpal region during the mineralization process. Here, we examined changes in the composition and structure of dentin using Raman spectroscopy on XLH human teeth, and using transmission electron microscopy on the dentin of Hyp mice (the murine model of XLH). The dentin of patients with XLH showed changes in the quality of the apatitic mineral, with greater carbonate substitution and lower crystallinity compared to the dentin of age-matched control teeth. In addition, ultrastructural analysis by transmission electron microscopy revealed a major disorganization of the peri- and intertubular structure of the dentin, with odontoblast processes residing within an unmineralized matrix sheath in the Hyp mouse. Taken together, these results indicate that like for bone and tooth cementum, there are impaired mineral quality and matrix changes in XLH dentin reflecting high sensitivity to systemic serum phosphate levels and possibly other local changes in the dentin matrix.