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甲状旁腺激素相关蛋白(PTHrP)和甲状旁腺激素/甲状旁腺激素相关蛋白受体1在正常及高钙血症模型大鼠切牙牙源性细胞中的表达

PTHrP and PTH/PTHrP receptor 1 expression in odontogenic cells of normal and HHM model rat incisors.

作者信息

Kato Atsuhiko, Suzuki Masami, Karasawa Yayoi, Sugimoto Tetsuro, Doi Kunio

机构信息

Safety Assessment Department, Chugai Pharmaceutical Co. Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan.

出版信息

Toxicol Pathol. 2005;33(4):456-64. doi: 10.1080/01926230590959604.

Abstract

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). We examined PTHrP and its receptor (PTHR1) expression patterns in odontogenic cells in normal and HHM model rat incisors. Nontreated nude rats serving as the normal control and HHM model rats produced by implantation of PTHrP-expressing tumor (LC-6) cells were prepared. HHM rats fractured its incisor, and histopathologically, restrict population of odontoblasts showed findings classified as "shortening of high columnar odontoblasts" and "dentin niche." The incisors were immunostained against PTHrP and PTHR1. In normal rats, PTHrP and PTHR1 colocalized in ameloblasts, cementoblasts, and odontoblastic cells from mesenchymal cells to columnar odontoblasts. In high columnar odontoblasts, PTHrP solely expressed. In the HHM animals, although the expression patterns were identical to those of the normal rats in normal area, the shortened high columnar odontoblasts maintained PTHR1 expression and dentin niche comprising odontoblastic cells expressed both proteins. In the HHM model, the protein expression patterns changed in the odontoblastic cells with histological anomalies, and thus direct relations between the anomalies and PTHrP/PTHR1 axis are suggested.

摘要

甲状旁腺激素相关肽(PTHrP)被发现是恶性肿瘤体液性高钙血症(HHM)的致病因素。我们检测了正常和HHM模型大鼠切牙成牙细胞中PTHrP及其受体(PTHR1)的表达模式。制备了作为正常对照的未处理裸鼠和通过植入表达PTHrP的肿瘤(LC-6)细胞产生的HHM模型大鼠。HHM大鼠的切牙发生骨折,组织病理学检查显示,成牙本质细胞数量受限,表现为“高柱状成牙本质细胞缩短”和“牙本质龛”。对切牙进行PTHrP和PTHR1免疫染色。在正常大鼠中,PTHrP和PTHR1共定位于成釉细胞、成牙骨质细胞以及从间充质细胞到柱状成牙本质细胞的成牙本质细胞。在高柱状成牙本质细胞中,仅表达PTHrP。在HHM动物中,尽管在正常区域的表达模式与正常大鼠相同,但缩短的高柱状成牙本质细胞维持PTHR1表达,而成牙本质细胞组成的牙本质龛则同时表达这两种蛋白。在HHM模型中,成牙本质细胞中的蛋白表达模式在组织学异常时发生改变,因此提示了这些异常与PTHrP/PTHR1轴之间的直接关系。

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