title: Histopathological study on the PTHrP-induced incisor lesions in rats.
abstract: Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.
authors.affiliation: Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan. katoath@chugai-pharm.co.jp
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kato
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Karasawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D003804:Dentin / Q000187:drug effects / Q000473:pathology; D007180:Incisor / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008954:Models, Biological; D009804:Odontoblasts / Q000187:drug effects / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D013997:Time Factors
chemical_list: D044162:Parathyroid Hormone-Related Protein