The cause of dentinal defects in heritable hypophosphatemic vitamin D-resistant rickets

低磷血症（Hyp）小鼠是人类x连锁低磷血症（XLH）的小鼠同源物，XLH是人类遗传性维生素d抗性佝偻病中最常见的形式，并已被用作人类XLH佝偻病的动物模型。与XLH相关的疾病的原因被认为主要是低磷血症，由刷状缘膜上的磷酸盐运输缺陷引起的肾磷酸盐重吸收受损引起。本研究的目的是分析低磷血症以外的几种疾病是否会导致Hyp小鼠局部牙本质缺陷。首先，我们比较了C57BL/6J Hyp/Y （Hyp）小鼠与C57BL/6J Hyp/Y雌性与C57BL/6J Hyp/Y雄性杂交获得的C57BL/6J +/Y （Nor）小鼠血清磷酸盐水平和牙本质特征。以野生型C57BL/6J +/Y （WT）小鼠为对照。尽管从统计学上看，Nor小鼠的血清磷酸盐水平低于WT小鼠，但在Nor小鼠的牙齿中未观察到Hyp小鼠的特征之一牙本质变宽。与此相反，Hyp小鼠的牙本质变宽，血清磷酸盐水平降低。我们的研究结果表明，Hyp小鼠的牙本质低矿化可能不仅仅是由低磷血症引起的。接下来，我们分析了Hyp和WT小鼠成牙细胞中OC蛋白和OC mRNA的分布和数量的差异。Hyp小鼠的OC在成牙细胞和牙本质中的分布与WT小鼠相同，但OC样免疫反应性较WT小鼠弱。另一方面，WT小鼠比Hyp小鼠更强烈地表达OC mRNA，这表明这种减少可能在Hyp小鼠牙本质中出现的低矿化中起作用。根据我们的研究结果，Hyp小鼠的牙本质低矿化可能不仅仅是由低磷血症引起的，还可能是由成牙细胞缺陷引起的，例如OC表达减少。

The hypophosphatemic (Hyp) mouse is a murine homolog of human X-linked hypophosphatemia (XLH), the most frequently occurring form of heritable vitamin D-resistant rickets in humans, and has been used as an animal model for human XLH rickets. The cause of disorders related to XLH is considered to be primarily hypophosphatemia resulting from impaired renal phosphate reabsorption arising from a defect in phosphate transport at the brush border membrane. The purpose of the present study was to analyze whether several disorders other than hypophosphatemia cause local dentinal defects in Hyp mice. First, we compared serum phosphate levels and dentinal features of C57BL/6J Hyp/Y (Hyp) mice with C57BL/6J +/Y (Nor) mice obtained by breeding C57BL/6J Hyp/+ females with C57BL/6J Hyp/Y males. Wild type C57BL/6J +/Y (WT) mice were used as control animals. Widened predentin, which is one of the features of Hyp mice, was not observed in the teeth of Nor mice, although, statistically, serum phosphate levels in the Nor mice were lower than in the WT mice. In contrast, Hyp mice showed both widened predentin and decreased serum phosphate levels. Our results suggest that the hypomineralizatior of dentin seen in Hyp mice may not be caused by hypophosphatemia alone.Next, we analyzed discrepancies in the distribution and quantity of OC protein and OC mRNA in odontoblasts between Hyp and WT mice. Hyp mice showed the same distribution of OC in odontoblasts and dentin as WT mice, however OC-like immunoreactivity in Hyp mice was weaker than in WT mice. On the other hand, WT mice expressed significantly OC mRNA more strongly than Hyp mice, suggesting that this reduction may have a role in the hypomineralization seen in the dentin of Hyp mice.Based on our findings, the hypomineralization of dentin in Hyp mice may not be caused by hypophosphatemia alone, but also by a defect in odontoblasts, such as the reduction of OC expression.