Disturbed tooth development in parathyroid hormone-related protein (PTHrP)-gene knockout mice
Disturbed tooth development in parathyroid hormone-related protein (PTHrP)-gene knockout mice
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DOI：
10.1016/s8756-3282(01)00669-x
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发表时间：
2002-01-01
期刊：
影响因子：
4.1
通讯作者：
Takano, Y
中科院分区：
文献类型：
--
作者：
Kitahara, Y;Suda, N;Takano, Y
甲状旁腺激素相关蛋白(PTHrP)参与多种组织器官发育过程中上皮细胞与间充质细胞的相互作用。牙胚发育是这种相互作用的经典模型。在牙胚中，PTHrP表达于釉质器官(上皮成分)，而其主要受体I型PTH/PTHrP受体表达于牙槽骨和牙囊细胞(间充质成分)。为了阐明PTHrP在胎儿牙胚发育中的作用，采用PTHrP基因敲除小鼠进行组织化学和超微结构分析。在野生型小鼠中，破骨细胞主要排列在发育中的牙胚周围的牙槽骨的内侧，贯穿胚胎晚期(胚胎后17.5天)和新生动物。相反，在PTHrP基因敲除纯合子胎鼠的相应区域中，成骨细胞占主导地位，只有偶尔的破骨细胞。在这些区域，经常可以观察到无细胞表面显示水泥线状的耐酒石酸酸性磷酸酶(TRAP)反应。在新生的纯合子小鼠中，骨针经常被显示穿透和/或压缩釉质器官，并导致牙胚的部分破坏。牙槽骨内侧破骨细胞数量较少，皱纹边缘不发达。牙胚本身细胞形态未见异常。在远离发育中的牙胚的骨表面，在纯合子小鼠中观察到结构特征类似于野生型小鼠的功能性破骨细胞。这些观察结果表明，PTHrP需要维持适当的骨细胞和破骨细胞的时空排列，这是牙胚和包裹牙胚的牙槽骨正常发育所必需的。观察还表明，PTHrP缺乏影响破骨细胞的结构和功能，仅影响位于生长牙胚附近的破骨细胞。(C)2002年，爱思唯尔科学公司。保留所有权利。
Parathyroid hormone-related protein (PTHrP) is involved in epithelial-mesenchymal cell interactions during development of various tissues and organs. Tooth germ development is a classical model for this interaction. In tooth germs, PTHrP is expressed in the enamel organ (epithelial component), whereas its major receptor, the type I PTH/PTHrP receptor is expressed in cells of the alveolar bone and dental follicle (mesenchymal components). To clarify the role of PTHrP during fetal tooth germ development, PTHrP gene-knockout mice were used for histochemical and ultrastructural analysis. In wild-type mice, osteoclastic cells were aligned predominantly in the inner aspects of the alveolar bone surrounding the developing tooth germs throughout the late embryonic (after embryonic, 17.5 days) and neonatal animals examined. In contrast, osteoblasts were predominant in corresponding areas of fetal homozygous PTHrP-gene knockout mice with only occasional osteoclasts. In such areas, cell-free surfaces showing cement line-like tartrate-resistant acid phosphatase (TRAP) reactions were frequently observed. In neonatal homozygous mice, bone spicules were often shown to penetrate and/or compress the enamel organ and caused partial destruction of the tooth germs. Osteoclasts were few in number in the inner aspects of the alveolar bone, and had poorly developed ruffled border. No morphological abnormality was noted in cells of the tooth germs proper. On bone surfaces away from developing tooth germs, functional osteoclasts with structural features similar to those in wild-type mice were observed in homozygous mice. These observations suggest that PTHrP is required to maintain an appropriate spatiotemporal arrangement of bone cells and osteoclast function, which are necessary for the normal development of tooth germ and alveolar bone encasing the tooth germ. The observation also demonstrates that PTHrP deficiency affects the structure and function of osteoclasts exclusively those located in the vicinity of the growing tooth germ. (C) 2002 by Elsevier Science Inc. All rights reserved.