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Toxicologic Pathology
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Articles

PTHrP and PTH/PTHrP Receptor 1 Expression in Odontogenic Cells of Normal and HHM Model Rat Incisors

Atsuhiko Kato1, Masami Suzuki1, Yayoi Karasawa1, Tetsuro Sugimoto1 and Kunio Doi2

1 Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., Gotemba-shi, Shizuoka 412-8513, Japan
2 Department of Veterinary Pathology, Faculty of Agriculture, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Correspondence: Address correspondence to: Dr. Atsuhiko Kato, Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan; e-mail:katoath{at}chugai-pharm.co.jp

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.

Key Words: PTHrP • PTH/PTHrP receptor 1 • HHM model • incisor • odontoblast • dentin • rats

Toxicologic Pathology, Vol. 33, No. 4, 456-464 (2005)
DOI: 10.1080/01926230590959604
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