Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation
Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation
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DOI：
10.1016/j.mod.2004.02.004
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发表时间：
2004-04-01
影响因子：
2.6
通讯作者：
Schipani, E
中科院分区：
文献类型：
--
作者：
Calvi, LM;Shin, HI;Schipani, E
甲状旁腺激素（Parathyroid hormone，PTH）相关蛋白（Parathyroid hormone related protein，PTH-rP）是一种重要的自分泌/旁分泌抑制剂，其表达仅限于牙齿发育的上皮层。PTH/PTHrP受体（PPR）mRNA在牙乳头中检测到，表明PTHrP和PPR可以调节上皮-间充质相互作用。为了探索可能的相互作用，我们研究了先前描述的转基因小鼠，其中组成型活性PPR靶向成骨细胞。这些转基因小鼠具有生动的出生后骨骼和牙齿表型，具有正常的牙齿萌出，但不正常，牙冠变宽。转基因mRNA表达首先在出生时在牙乳头中检测到，出生后1周，在成牙本质细胞中检测到。在成釉细胞或其他上皮结构中没有转基因表达。产前，转基因臼齿和门牙没有显着变化。1周龄时，牙乳头增宽，成牙本质细胞层紊乱，牙本质基质减少。此外，牙尖数目异常增加，成釉细胞层紊乱，釉质基质减少。成牙本质细胞和成釉细胞的细胞分化，令人惊讶的是受损，如原位杂交和电子显微镜所示。有趣的是，Sonic Hedgehog的成釉细胞表达，成釉细胞细胞分化的主要决定因素，在转基因磨牙中发生了显着改变。这些数据表明，成牙本质细胞激活的PPR可能发挥了重要作用，在终端成牙本质细胞，间接，成釉细胞分化，并描述了一个有用的模型来研究这种新的行动的PPR可能会调节间充质/上皮细胞的相互作用在牙齿形态发生和发育的后期阶段。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Parathyroid hormone (PTH)-related protein (PTH-rP) is an important autocrine/paracrine attenuator of programmed cell differentiation whose expression is restricted to the epithelial layer in tooth development. The PTH/PTHrP receptor (PPR) mRNA in contrast is detected in the dental papilla, suggesting that PTHrP and the PPR may modulate epithelial-mesenchymal interactions. To explore the possible interactions, we studied the previously described transgenic mice in which a constitutively active PPR is targeted to osteoblastic cells. These transgenic mice have a vivid postnatal bone and tooth phenotype, with normal tooth eruption but abnormal, widened crowns. Transgene mRNA expression was first detected at birth in the dental papilla and, at 1 week postnatally, in odontoblasts. There was no transgene expression in ameloblasts or in other epithelial structures. Prenatally, transgenic molars and incisors revealed no remarkable change. By the age of 1 week, the dental papilla was widened, with disorganization of the odontoblastic layer and decreased dentin matrix. In addition, the number of cusps was abnormally increased, the ameloblastic layer disorganized, and enamel matrix decreased. Odontoblastic and, surprisingly, ameloblastic cytodifferentiation was impaired, as shown by in situ hybridization and electron microscopy. Interestingly, ameloblastic expression of Sonic Hedgehog, a major determinant of ameloblastic cytodifferentiation, was dramatically altered in the transgenic molars. These data suggest that odontoblastic activation of the PPR may play an important role in terminal odontoblastic and, indirectly, ameloblastic cytodifferentiation, and describe a useful model to study how this novel action of the PPR may modulate mesenchymal/epithelial interactions at later stages of tooth morphogenesis and development. (C) 2004 Elsevier Ireland Ltd. All rights reserved.