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是人类最常见的可遗传维生素D抗性软骨病形式，已被用作人类XLH型软骨病的动物模型。与XLH相关的疾病的原因被认为主要是由于刷状缘膜磷酸盐运输缺陷而导致的肾脏磷酸盐重吸收受损所致的低磷血症。本研究的目的是分析除低磷血症以外的其他几种疾病是否会导致Hyp小鼠的局部牙本质缺陷。首先，我们比较了C57BL/6J Hyp/Y(Hyp)小鼠和C57BL/6J+/Y(NOR)小鼠的血磷水平和牙本质特征。以野生型C57BL/6J+/Y(WT)小鼠为对照。尽管从统计学上讲，NOR鼠的血磷水平低于WT鼠，但NOR鼠的牙齿中没有观察到增宽的前牙本质，这是Hyp鼠的特征之一。相比之下，Hyp小鼠表现出前牙本质增宽和血清磷水平下降。我们的结果表明，Hyp鼠牙本质的低矿化可能不是由低磷血症引起的。接下来，我们分析了Hyp和WT小鼠成牙本质细胞中OC蛋白和OC mRNA的分布和数量的差异。Hyp小鼠OC在成牙本质细胞和牙本质中的分布与WT小鼠相同，但其OC样免疫反应弱于WT小鼠。另一方面，WT小鼠OC mRNA的表达明显强于Hyp小鼠，提示这种减少可能与Hyp鼠牙本质中的低矿化有关。根据我们的发现，Hyp小鼠牙本质的低矿化可能不仅仅是由于低磷血症，还可能是成牙本质细胞的缺陷，如OC表达的减少。

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.