The purpose of the present study was to clarify kinetic aberrations and premalignant and malignant lesions of oral mucosa. Epithelial hyperplasia (EH), mild and moderate epithelial dysplasia (ED), carcinoma in situ (CIS), and squamous cell carcinoma (SCC) were evaluated for histone H3 mRNA, p53 protein (P53), cyclin D1, and cyclin B1. A few cases were positive for P53 and histone H3, but rarely coexpressed both in EH and ED. In CIS and SCC, increased expressions of P53 and histone H3 were seen, and there were also many cases showing extensive co-expression of both. There were many cyclin D1-positive cases of EH and ED. In CIS and SCC, increased numbers of cyclin D1-positive and cyclin B1-positive cells were apparent, and these cells were distributed widely. In cases of CIS with co-expression for histone H3 and P53, there was increased and wide distribution of cyclin D1- and cyclin B1-positive cells. These features of CIS may indicate that cell proliferation is induced, and that zonal differentiation of stratified squamous epithelium is irregular as seen in SCC.

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In order to examine effects of β-tricalcium phosphate (TCP) or carbonate apatite particles (CAP) in bone repair, we studied bone healing processes histopathologically and immunohistochemically in rat parietal bone defects filled with TCP or CAP. Without TCP or CAP filling, the bone repair was carried out by osteoblasts derived from the edge of the bone defect but did not occur at the center area of the defect. However, with TCP or CAP filling, conductive bone formation occurred along the surfaces of both particles, indicating that those ceramics definitely induced osteoblastic differentiation, which was confirmed by immunohistochemical expressions of such osteoblastic differentiation markers as BMP2/4, Runx2 and Osterix. The expressions of BMP2/4 preceding those of the other osteoblastic markers seemed to be essential for the conductive bone formation by calcium phosphate ceramics. Osteoblastic cells on these particles were derived from resting osteoblasts on the remaining bone surface. Type I collagen, dentin matrix protein 1, and osteocalcin were also expressed in osteoblastic cells as well as in the bone matrix, suggesting that these molecules participated in both bone formation and regulation of osteoblastic differentiation.

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Chitosan stimulates the fibroblastic, endothelial, and intestinal epithelial cells to release chemotactic inflammatory cytokines, especially interleukin 8 (IL-8). Tannic acid (TA) has a variety of biological activities, such as anti-inflammatory, anti-viral effects. However, the pre-treatment of TA on chitosan polymer-induced IL-8 production from epithelial cells has not been well studied. This study focused on the effect of TA on chitosan polymer-induced IL-8 production in the oral mucosal epithelium as estimated by HSC-2 cells established from a human oral squamous cell carcinoma. The intracellular IL-8 production was measured by flow cytometry. The chitosan polymer-induced production of IL-8 decreased after pre-treatment with TA. IL-8 mRNA was measured by real-time PCR, and its mRNA expression level was reduced after TA pre-treatment. Antibody-based assays were used to investigate the effect of chitosan and TA on the activation of mitogen-activated protein kinases (MAPKs). These investigations showed the pre-treatment effects of TA on IL-8 production to be mainly mediated through the inhibition of the p38 MAPK pathways. The present study demonstrated that TA pre-treatment reduced the intracellular IL-8 production in HSC-2 cells via the MAPK signaling pathways. These findings indicate that the combined application of TA and chitosan may be clinically beneficial for the inflammatory lesions of the oral mucosa.

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The aim of this study was to examine the effect of centrifugal force on rat bone marrow osteoblast-like cells (RBM) in vitro. RBM were seeded and cultured for 2 days. Centrifugal forces were added to the cells in the culture dishes using a centrifuge for 20 min either at 600 rpm or 4,800 rpm. The cells without centrifugation were used as control. The expression of HSP27 mRNA of both experimental groups after addition of centrifugal force for 3 hrs was significantly up-regulated compared with the control group. In the 4,800 rpm groups, the cells showed contracted shapes compared to the controls and the 600 rpm groups after treatment with centrifugal force. The maximum height of each cell in the control group was 2.00 ± 0.33 μm. The maximum height of each cell in the 600 rpm group was 1.50 ± 0.23 μm, and in the 4,800 rpm group it was 1.13 ± 0.23 μm. The proliferation ratio in the 4,800 rpm group at day 3 was significantly higher than in the other group. The expression of type I collagen and alkaline phosphatase (ALP) mRNAs in both experimental groups increased at earlier time periods compared to the control groups. ALP activity revealed no significant difference between the experimental groups and the control group. A centrifugal force of 4,800 rpm might promote the proliferation and early differentiation of rat bone marrow cells.

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Since the risks of development of salivary mucoepidermoid carcinoma and Warthin tumor have been significantly greater among atomic bomb survivors in a dose-dependent manner, the p53 gene, an important proto-oncogene whose mutation has been related to radiation, was analyzed by DNA sequencing and immunohistochemistry in 37 cases of mucoepidermoid carcinoma collected from Niigata and Nagasaki and in 33 cases of Warthin tumor collected from Niigata. Immunohistochemically, p53 gene products were heavily demonstrated in most of the tumor cell nuclei of mucoepidermoid carcinomas but not in Warthin tumors. Mucoepidermoid carcinomas had some point mutations (codons 136-137, 144, 232, 234, and 241) but their incidences among the samples were not significantly high (2.7%-10.8%). In contrast, three point mutations (codons 143, 151, and 229) were commonly found in the Warthin tumor cases (80%-87%), but the former two mutations did not alter their amino acid composition. Thus, there were no p53 mutations which were shared by the two tumors. However, the mutations at exon 5 of mucoepidermoid carcinomas were significantly higher in the cases from Nagasaki than those from Niigata, although their highest frequencies at most were around 10%. The results suggest that point mutations of p53 gene, as far as exons 5-7 were concerned, do not play any obviously important roles in the radiation-based tumorigenetic processes shared by mucoepidermoid carcinoma and Warthin tumor.

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