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

遗传性低磷血症维生素D抵抗性佝偻病牙本质缺损的原因

基本信息

批准号：
11470450
负责人：
OOSHIMA Takashi
金额：
$ 7.23万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

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.

低磷酸盐血症（Hyp）小鼠是人类X连锁低磷酸盐血症（XLH）的小鼠同源物，XLH是人类中最常见的遗传性维生素D抗性佝偻病形式，并已用作人类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由于刷状缘膜磷酸盐转运缺陷引起的肾磷酸盐重吸收受损导致的低磷酸盐血症。本研究的目的是分析几种疾病以外的低磷酸盐血症是否会导致局部牙本质缺陷的Hyp小鼠。首先，我们比较了C57 BL/6 J Hyp/Y（Hyp）小鼠与C57 BL/6 J Hyp/+雌性与C57 BL/6 J Hyp/Y雄性交配获得的C57 BL/6 J +/Y（Nor）小鼠的血清磷酸盐水平和牙本质特征。野生型C57 BL/6 J +/Y（WT）小鼠用作对照动物。加宽的前牙本质，这是Hyp小鼠的特征之一，在Nor小鼠的牙齿中没有观察到，尽管在统计学上，Nor小鼠的血清磷酸盐水平低于WT小鼠。相比之下，Hyp小鼠表现出增宽的前牙本质和降低的血清磷酸盐水平。我们的研究结果表明，Hyp小鼠牙本质矿化不良可能不是单纯的低磷血症引起的。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Hyp小鼠OC样免疫反应性弱于WT小鼠。另一方面，野生型小鼠OC mRNA的表达明显强于Hyp小鼠，这表明这种减少可能在Hyp小鼠牙本质中看到的矿化不足中起作用，根据我们的研究结果，Hyp小鼠牙本质的矿化不足可能不仅仅是由低磷酸盐血症引起的，还可能是由成牙本质细胞的缺陷，如OC表达的减少。