Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.
Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.
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DOI：
10.1016/j.bone.2004.06.016
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发表时间：
2004-11
期刊：
影响因子：
4.1
通讯作者：
Y. Kitahara;N. Suda;T. Terashima;O. Baba;K. Mekaapiruk;V. Hammond;Y. Takano;K. Ohyama
中科院分区：
文献类型：
--
作者：
Y. Kitahara;N. Suda;T. Terashima;O. Baba;K. Mekaapiruk;V. Hammond;Y. Takano;K. Ohyama
我们以前的研究表明，在胚胎晚期[晚于胚胎第17.5天（E17.5）]和新生纯合子甲状旁腺相关蛋白（PTHrP）敲除小鼠的牙胚被周围的牙槽骨组织挤压或穿透。体内和体外研究表明，牙胚本身的发育没有受到干扰，但由于破骨细胞数量减少和功能低下导致的牙槽骨吸收不足是这种异常的主要原因。除了牙槽骨吸收不足外，在纯合子小鼠中观察到牙胚的骨形成，这表明加速的骨形成也有助于这种异常。为了进一步研究这一点，在E14.0和E15.5纯合子小鼠，当牙槽骨形成时，用于组织化学和骨组织形态计量学分析。与胚胎晚期相反，在E14.0纯合子小鼠中，牙槽骨尚未压缩发育中的牙胚，但与野生型同窝小鼠相比，观察到更大量的骨组织。在E14.0骨组织形态计量学分析表明，成骨细胞的数量和表面的下颌骨和股骨的骨领的纯合子小鼠显着高于野生型小鼠。然而，与我们先前的研究显示纯合子小鼠E18.5的破骨细胞表面显著低于野生型小鼠不同，E14.0的这项研究显示两种基因型之间没有显著差异。为了评估牙胚周围的钙化量，从野生型和突变小鼠的钙黄绿素标记切片重建下颌骨的3D图像。在E14.0进行标记，并在钙黄绿素注射后1小时处死小鼠以使骨吸收的影响最小化。三维图像的比较显示，标记的表面是更大的周围发育的牙胚在纯合子小鼠比野生型小鼠。在E15.5天，成骨细胞接近纯合子小鼠的釉质器官，但在野生型小鼠中未观察到。在这项研究中，我们报告了成骨细胞数量的系统性增加和加速骨形成的纯合子PTHrP基因敲除小鼠，这两者都有助于牙齿发育异常。
Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development.