Search

Homeobox genes play important roles in craniofacial morphogenesis. However, the characteristics of the transcription factor Hoxc during palate formation remain unclear. We examined the immunolocalization patterns of Hoxc5, Hoxc4, and Hoxc6 in palatogenesis of cleft palate (Eh/Eh) mice. On the other hand, mutations in the FGF/FGFR pathway are exclusively associated with syndromic forms of cleft palate. We also examined the immunolocalization of Fgfr1 and Erk1/2 to clarify their relationships with Hoxc in palatogenesis. Some palatal epithelial cells showed Hoxc5 labeling, while almost no labeling of mesenchymal cells was observed in +/+ mice. As palate formation progressed in +/+ mice, Hoxc5, Hoxc4, and Hoxc6 were observed in medial epithelial seam cells. Hoxc5 and Hoxc6 were detected in the oral epithelium. The palatal mesenchyme also showed intense staining for Fgfr1 and Erk1/2 with progression of palate formation. In contrast, the palatal shelves of Eh/Eh mice exhibited impaired horizontal growth and failed to fuse, resulting in a cleft. Hoxc5 was observed in a few epithelial cells and diffusely in the mesenchyme of Eh/Eh palatal shelves. No or little labeling of Fgfr1 and Erk1/2 was detected in the cleft palate of Eh/Eh mice. These findings suggest that Hoxc genes are involved in palatogenesis. Furthermore, there may be the differences in the localization pattern between Hoxc5, Hoxc4, and Hoxc6. Additionally, Hoxc distribution in palatal cells during palate development may be correlated with FGF signaling. (228/250 words) © 2016 Japanese Teratology Society.

Mouse embryos exposed to 2,3,7,8-tetrachloridedibenzo-p-dioxin (TCDD) develop cleft palates and hydronephrosis. Cleft palates occur after TCDD exposure due to contact and/or fusion failure. We investigated whether cleft palate can be induced by dissociation of the palatine process after fusion. Pregnant mice on gestational day (GD) 12 were randomly divided into two groups: one group was administered through gastric tubes one dose of olive oil (control group) and the other group was administered one dose of TCDD diluted with olive oil, both at a dose of 40 microg/kg body weight. Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 13-18) and the palatal form was observed using a stereoscopic microscope. In TCDD-exposed embryos, palatal fusion was observed on GD 14, 15 and 16 and the incidence of cleft palate was 100% on GD 18. Fusion rates were 17.5 +/- 15.2% and 12.4 +/- 11.8% on GD 15 and 16, respectively. Some palates from the TCDD-exposed mouse embryos showed clearly developed cleft palate after fusion of the lateral palatine processes during palatal formation. A mass of cells, which were chiefly epithelial in the fused palates was observed in the TCDD-exposed mouse embryos. A decrease in E-cadherin expression was observed in this mass of cells, indicating its involvement in the development of cleft palate.

Objectives and design: The expressions of human beta defensin-1 (HBD-1), -2 (HBD-2) and -3 (HBD-3) in non-inflamed pseudocysts such as mucoceles were investigated immunohistochemically in this study. Materials and methods: Mucocele specimens were obtained from 21 patients. The expression of HBDs was studied immunohistochemically by using antibodies directed against HBD-1, -2, and -3. Statistical analyses were carried out on serial sections stained with antibodies. Results: Cells expressing HBDs were found in mucoceles. The expression of HBD-2 was observed in floating cells in all the specimens, whereas HBD-1 and HBD-3-expressing cells were detected in 93% and 73% of the mucoceles, respectively. The HBD-2 signal was the most intense and the HBD-3 signal intensity was weaker than that of HBD-1. HBDs were expressed in neutrophils and in other floating cells. Interestingly, the signal intensity and the population of positive cells located close to the centers of cysts were higher than those located in the peripheral areas of cysts. Conclusion: The expression of HBDs was found even in non-inflamed pseudocysts such as mucoceles. These results suggest that an unknown mechanism not involved in biophylaxis for the expression of HBDs may exist.

Morphological and immunohistological examinations were performed to reveal the mechanisms of cleft palate induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ICR strain mice 8-10 weeks of age were used in the study. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 40 microg/kg. From GD 13.5 to 16.5, palates were examined by scanning electron microscopy (SEM), hematoxyline-eosin (HE) staining, and immunohistochemical staining of FGFR1/2, TGF-beta3, MSX1 and LHX8. In the control group, both of the palatal shelves began elevating on GD 14.0 and finished within 6 h. After the elevation, all of the shelves had completely fused with each other on GD 14.5. In the TCDD-treated group, palatal shelves elevated 1 day later than in the control group. However, all palates had elevated by GD 15.0. After the elevation, the shelves contacted each other and fused; however, they were separated on GD16.0. HE staining showed that medial edge epithelium (MEE) was thinner in the TCDD group than in the control group. MEE observed under a high magnification (x2500) exhibited filopodia-like filaments and the cells were bulged in the control group. In contrast, in the TCDD group, no filaments were observed and the cells were flat with unclear boundaries. Immunohistologically, there were no characteristic findings except for FGFR1. FGFR1 was not expressed in the TCDD group after the fusion phase (GD 14.5). TCDD induces many morphological and molecular changes to MEE cells and causes cleft palates.

OBJECTIVES AND DESIGN: It has been previously reported that α-defensin (HNPs) and β-defensin-2 (HBD-2) peptides with antifungal and cytotoxic activities can be detected in oral carcinomas and the saliva of patients with oral carcinomas. The present study investigated the presence of HNPs and HBD-2 in oral epithelia with candidiasis. MATERIALS AND METHODS: Tissue sections (4 μm) were prepared from biopsy and surgically removed specimens diagnosed as oral candidiasis (n=10). The sections were examined immunohistochemically with antibodies directed against HNPs and HBD-2. RESULTS: Tissue sections of oral candidiasis were immunostained with antidefensin antibodies. Neutrophils in the inflamed lamina propria were positively immunostained with anti-HNPs antibody. The cytoplasm of cells in the upper spinous layer, in the lower spinous layer and in the parakeratinized layer of buccal epithelia with candidiasis was immunostained intensely with anti-HBD-2 antibody. In contrast, the expression of HBD-2 in the normal spinous layer was much weaker than that in oral candidiasis. No signals of HNPs were found in normal buccal epithelium. CONCLUSION: Buccal specimens from individuals with oral candidiasis show greater levels of expression of both HNPs and HBD-2. There might be a dual protection manner by defensins against fungal inflammation in infected buccal epithelia locally. Generally, HBD-2 signals have been found everywhere in the buccal epithelium; however, in an infected area, the signal intensity of HBD-2 has increased. HNPs signals have not been found in the normal buccal epithelium; however, HNPs signals have increased when the infection occurred.

Grafted periosteum is known to have potential for heterotopic bone formation by endochondral ossification. Although osteochondrogenic cells have been thought to originate from the osteogenic layer in grafted periosteum, no histological report has yet demonstrated this. The present study was designed to elucidate the origin of chondrogenesis preceding bone formation in grafted periosteum. Periostea harvested from young Japanese white rabbits' tibiae were grafted into suprahyoid muscles and examined radiographically and histologically at postoperative days 1, 7, 9, 14, 21, and 35. Normal periostea and tibial graft site were also examined. Surgical harvesting of the periosteum split and damaged its osteogenic layer but retained the fibrous layer intact. Most of the osteoblasts remained on the tibial bone surface, and only few cells of the osteogenic layer were present in grafted tissue. By the seventh day after grafting, the fibrous layer had thickened. The fibroblastic cells in the fibrous layer had significantly increased in number (P < 0.01) and were positively stained for proliferating cell nuclear antigen. These cells exhibited alkaline phosphatase activity at day 9. The differentiated chondrocytes had formed cartilage at postoperative day 14. Cells in the osteogenic layer appeared necrotic and subsequently disappeared. Following postoperative day 21, cartilage was replaced by trabecular bone. Bone formation was completed by 35 days. An X-ray analysis at this time also revealed new bone formation. These findings indicate that grafted periosteum forms bone by endochondral ossification and that the cells of the fibrous layer play essential roles in chondrogenesis that precedes such bone formation. Anat Rec 264:348–357, 2001. © 2001 Wiley-Liss, Inc.

Background: Erdheim–Chester disease is a rare histiocytic disease entity related to juvenile xanthogranuloma. It is a systemic condition, usually occurs in adult, characterized by infiltration of foamy histiocytes within the bone and soft tissues. Methods and results: We report a case of 13-year-old female patient who first presented with multiple osteolytic lesions of the jaws followed by bilateral symmetrical bone lesions affecting the lower extremities, as well as brain and abdominal involvement. Histological findings of the jaw lesions showed lipid-storing CD68 (+), CD1a (−) histiocytes with Touton type giant cells. Conclusion: To the best of our knowledge, this is the first case of Erdheim–Chester disease with jaw bone lesions occurring as initial presenting symptom.

We examined a patient with cleidocranial dysplasia (CCD) and cleft lip and found a new stop codon mutation in CBFA1. This mutation was a heterozygous C-to-T transition in exon 3 of CBFA1. This nucleotide change converts a CAA codon to a TAA (stop) codon at amino acid position Gln195 in the runt domain of CBFA1.