Aberrant cementum phenotype associated with the hypophosphatemic hyp mouse.

Cementogenesis is sensitive to altered local phosphate levels; thus, we hypothesized a cementum phenotype, likely of decreased formation, would be present in the teeth of X-linked hypophosphatemic (Hyp) mice. Mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex) cause X-linked hypophosphatemia, characterized by rickets, osteomalacia, and hypomineralized dentin formation, a phenotype recapitulated in the Hyp mouse homolog. Here, we report a developmental study of tooth root formation in Hyp mouse molars, focusing on dentin and cementum. Light and transmission electron microscopy were used to study molar tissues from wild-type (WT) and Hyp mice. Demineralized and hematoxylin and eosin–stained tissues at developmental stages 23 to 96 days postcoital (dpc) were examined by light microscopy. Immunohistochemistry methods were used to detect bone sialoprotein (BSP) distribution in Hyp and WT mouse molar tissues, and transmission electron microscopy was used to study similar molar tissues in the non-demineralized state. Dentin in Hyp mice exhibited mineralization defects by 33 dpc, as expected, but this defect was partially corrected by 96 dpc. In support of our hypothesis, a cementum phenotype was detected using a combination of immunohistochemistry and transmission electron microscopy, which included thinner BSP-positive staining within the cementum, discontinuous mineralization, and a globular appearance compared to WT controls. Mutations in the phosphate-regulating Phex gene of the Hyp mouse resulted in defective cementum development.

牙骨质生成对局部磷酸盐水平的改变敏感；因此，我们假设在X连锁低磷血症（Hyp）小鼠的牙齿中会出现一种牙骨质表型，很可能是形成减少。X染色体上与内肽酶具有同源性的磷酸盐调节基因（Phex）发生突变会导致X连锁低磷血症，其特征为佝偻病、骨软化以及矿化不足的牙本质形成，这种表型在Hyp小鼠同源物中重现。在此，我们报道了对Hyp小鼠磨牙牙根形成的一项发育研究，重点关注牙本质和牙骨质。 使用光学显微镜和透射电子显微镜研究野生型（WT）和Hyp小鼠的磨牙组织。通过光学显微镜检查交配后23至96天（dpc）发育阶段的脱矿以及苏木精 - 伊红染色组织。使用免疫组织化学方法检测Hyp和WT小鼠磨牙组织中骨涎蛋白（BSP）的分布，并使用透射电子显微镜研究未脱矿状态下的类似磨牙组织。 如预期的那样，Hyp小鼠的牙本质在33 dpc时表现出矿化缺陷，但到96 dpc时该缺陷得到了部分纠正。为支持我们的假设，通过免疫组织化学和透射电子显微镜相结合的方法检测到一种牙骨质表型，与WT对照组相比，包括牙骨质内较薄的BSP阳性染色、不连续矿化以及呈球状外观。 Hyp小鼠的磷酸盐调节Phex基因发生突变导致牙骨质发育缺陷。