Circling behavior developed in Dmp1 null mice is due to bone defects in the vestibular apparatus.

Circling behavior developed in Dmp1 null mice is due to bone defects in the vestibular apparatus.
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DOI:
10.7150/ijbs.6.537
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发表时间:
2010-09-15
影响因子:
9.2
通讯作者:
Feng JQ
Feng JQ
中科院分区:
生物学2区
文献类型:
--
作者:
Lv K;Huang H;Lu Y;Qin C;Li Z;Feng JQ

文献摘要

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随着年龄的增长,身体平衡功能逐渐丧失。然而,骨质疏松症对身体平衡的潜在影响在很大程度上尚不清楚。牙本质基质蛋白 1 (DMP1) 在骨中高表达,是磷酸盐稳态和矿化所必需的。 Dmp1 缺失小鼠显示出明显的骨结构缺陷。在这项研究中,我们报告了 Dmp1 缺失小鼠的转圈行为和对触摸的过度反应。我们的组织学、抗酒石酸酸性磷酸酶 (TRAP) 染色和 µCT 数据显示前庭器 Dmp1 无孔骨结构中的巨大变化,例如矿化不良基质的扩张。 DMP1 缺失骨中 DMP1 的靶向重新表达不仅完全挽救了骨表型,而且还挽救了绕圈行为和过度反应。此外,X-gal染色和DMP1免疫组织化学检测显示,DMP1在内耳神经元细胞或平衡相关细胞中不表达,表明内耳骨迷路缺陷间接导致转圈行为和/或对触摸的过度反应。最后,周细胞样细胞中 DMP1 lacZ 信号的发现可能表明 DMP1 在血管生成中的新功能。
With age, there is a progressive loss of body balance function. Yet, the potential influence of osteoporosis on body balance is largely unknown. Dentin matrix protein 1 (DMP1) is highly expressed in bone and required for phosphate homeostasis and mineralization. Dmp1 null mice display striking defects in bone structure. In this study we reported circling behavior and hyper reaction to touching in Dmp1 null mice. Our histology, tartrate resistant acid phosphatase (TRAP) staining and µCT data showed dramatic changes, such as an expansion of poorly mineralized matrices, in the Dmp1 null porous bony structure in the vestibular apparatus. The targeted re-expression of DMP1 in the Dmp1 null bone fully rescued not only the bone phenotype, but also circling behavior and hyper reaction. Furthermore, X-gal stain and DMP1 immunohistochemistry assay showed that DMP1 was not expressed in neuron cells or balance related cells in the inner ear, suggesting that a defect in the bony labyrinth of the internal ear is indirectly responsible for the circling behavior and/or hyper reaction to touching. Finally, discovery of DMP1 lacZ signal in pericyte-like cells may suggest a new function of DMP1 in angiogenesis.