Dry mouth promotes dental caries, disorders of eating and swallowing, and aspiration pneumonia, which result in remarkable decrease of quality of life (QOL) in severe cases. Cell transfer therapy using stem cells is a promising treatment for the patients suffering from severe dry mouth due to the ability of reconstituting damaged glands. Stem cells are classified into three groups: tissue stem cells, embryonic stem cells (ES cells), and induced pluripotent stem cells (iPS cells). To date, it is reported that salivary stem cells can recover the hypofunction of salivary glands, which is mediated through not only reconstituting the glands but also soluble factors in a paracrine manner. We have focused on a cell population called “side population (SP)” cells, which can be isolated without using a cell surface marker. Since their first isolation from bone marrow as a fraction containing a high frequency of stem cells, SP cells have been analyzed in a variety of organs. In the present study, we investigated the effects of experimental treatment with SP cells using a mouse model of irradiationinduced salivary gland dysfunction, and the possibility of establishing a treatment approach with a specific factor expressed in SP cells.

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With the society aging and birthrate declining, tissue engineering for irreversible skeletal damages attracts a great deal of attentions. Although there are several different scaffolds available for skeletal reconstruction, clinicians are not satisfied with their performance. By focusing on shape compatibility of the scaffolds, we have successfully controlled 3D shape of the calcium phosphate-based biomaterials on a millimeter to micrometer scale by inkjet printing and injection molding technologies and thereby developed new artificial bones. By designing and combining tetrahedron-like macromers with mutually reactive end groups, we have successfully developed high-strength hydrogels with extremely homogeneous network structure for artificial cartilage and intervertebral disc. By precisely controlling 3D shape on various scales, it is possible to dramatically enhance the performance of biomaterials. Combination of such biomaterials with bioactive factors will provide appropriate treatment for a large number of patients with skeletal defects.

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In the past several years, the importance of microRNA (miRNA) in cancer cells has been recognized. Proper control of miRNA expression is essential for maintaining a steady state of the cellular machinery. Dysregulation of miRNAs leads to the cancer development, meaning that expression profile of miRNAs can be used as cancer biomarker, and recovery of down-regulated miRNAs or inhibition of up-regulated miRNAs will be a novel approach for cancer therapy. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients. Most of the circulating miRNAs are included in protein, lipid or lipoprotein complexes, such as RNA-binding proteins, apoptotic bodies, microvesicles, or exosomes, and are, therefore, highly stable. The existence of circulating miRNAs in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function, as well as the meaning of the existence of extracellular miRNAs, remain largely unclear. Our recent study revealed the secretory mechanism of miRNAs and showed their cell-to-cell transfer. Here we summarize current approaches to modulate the intercellular and interindividual network via silencing signals exported by secretory miRNAs and discuss about the usage of circulating miRNAs as a novel communication tool.

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Problem-based learning (PBL) derives from the principle that problems can be used as the starting point for acquiring new knowledge. In 2003, this method was introduced to dental education in Showa University School of Dentistry, as part of a wave of dynamic changes to the educational style, from teacher- to learner-centered education. Faculty members invested substantial time and effort in adopting and integrating PBL into the dental curriculum, and PBL is now used as the major method for the interdisciplinary education of first- to sixth-year students of 4 schools (Medicine, Dentistry, Pharmacy, and Nursing and Rehabilitation Sciences). In this review, I first describe the history of PBL in Showa University School of Dentistry, and then evaluate the role of PBL in future dental education.

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Many pathological and physiological traits of the craniofacial region are inheritable. We have investigated the genetic basis underpinning certain aspects of craniofacial development and of specific pathological conditions that lead to malocclusion. A better understanding of normal and pathologic processes will give us an enhanced ability to diagnose and resolve problems. We have found in two separate families that primary failure of tooth eruption (PFE), a rare autosomal dominant disorder, is the result of a variants of the type 1 parathyroid hormone receptor (PTH1R). This receptor coordinates tooth eruption by regulating osteoclastogenesis via the release of receptor activator of nuclear factor-κB ligand (RANKL) from periodontal ligament cells. It is discussed the evidence for genetic traits in normal craniomaxillofacial morphology and in prognathism, by using genetic testing to identify patients at risk of mandibular growth abnormalities and to facilitate early and effective diagnosis of their treatment needs. It is also briefly discuss evidence for genetic determination of tooth morphology, notably the role of the ectodysplasin A receptor (EDAR) gene in the development of ‘shovel-shaped’ incisors in certain populations, including Japanese. The advent of genome-wide association studies has enabled us to explore the genetic basis of development in the orofacial region, and patients are increasingly positive about the role of genetics in improving the predictability of orthodontic diagnosis and treatment. Therefore, genetics taking a predominant role in orthodontics in the near future is envisaged.

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The aim of this study was to find a method for the elderly to cope with xerostomia and oral dryness. In particular, we investigated whether daily oral health care with a dentifrice that included a moisturizing agent could affect oral dryness. The subjects were 10 elderly women (mean age was 80.1 years old) who resided in a nursing home and were using a dentifrice that contained a moisturizing agent for daily oral health care. After three months of the beginning of using a dentifrice, the participants were classified into 2 groups, 5 women who continued to use the dentifrice and the others who stopped using the dentifrice for two months. An oral dryness evaluation was carried out with an oral mucosal moisture measurement and a saliva wetness test at the beginning of use of the dentifrice, three months and five months later. The oral mucosal moisture measurement of buccal and tongue mucosa indicated a significant improvement after 3 months of continued use of the dentifrice. However, all participants who had stopped using the dentifrice reverted to their prior oral dryness condition after five months. In the dentifrice group there was almost no variation for two months. These results show that application of a dentifrice with an oral moisturizing agent could improve the oral dryness of the elderly. When the elderly stop using the dentifrice, multidirectional intervention could be needed for fundamental improvement of oral dryness and xerostomia.

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To clarify whether Pam3CSK4, a TLR2 agonist, induces the differentiation of osteoclasts, we investigated the osteoclastogenesis and gene expression induced by Pam3CSK4 in RAW264.7 monocyte/macrophage cells. We found that 1 μg/ml Pam3CSK4 induced osteoclastogenesis without adding RANKL exogenously, whereas 1 μg/ml LPS (Re mutant), a ligand for TLR4, failed to produce osteoclasts in RAW 264.7 cells. The number of TRAP-positive multinuclear cells in the Pam3CSK4 group (156.2 +/− 26.5 cells/well) was significantly (p<0.01) less than that of 100 ng/ml RANKL (196.5 +/− 32.0 cells/well), which was a positive control. Quantitative real-time RT-PCR analysis showed that i) the gene expression levels of TRAP, cathepsin K and matrix metalloproteinase 9, which are osteoclast differentiation markers, were upregulated (p<0.01) by both RANKL and Pam3CSK4, whereas LPS did not increase gene expression of TRAP or cathepsin K, ii) the expression level of RANK was decreased significantly (p<0.01) by both Pam3CSK4 and LPS, but increased by RANKL, iii) the expression levels of TNFα and IL-6, inflammatory cytokines, were upregulated significantly (p<0.01) by both Pam3CSK4 and LPS and iv) the expression level of RANKL was similar to that of other experimental groups in RAW 264.7 cells (p>0.05). Collectively, these results indicate that Pam3CSK4, but not LPS, induces osteoclastogenesis in RAW 264.7 cells in the absence of exogenous RANKL.

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The aim of this study was to consolidate oral health management systems in the acute stages. The practical status of oral health in perioperative patients and improvements achieved through coordinated oral health care were investigated. Subjects of the present study were 87 patients who underwent oral intubation in the intensive care unit (ICU). These patients attended an oral health care center from October 2010 to March 2011. Dentists rated the oral status of subjects within 24 h of admission to the ICU on a three-point scale by assessing the lips, teeth, mucous membrane, gingiva, tongue, and saliva. In addition, the number of Candida colonies detected on the tongue was noted at initial assessment. At initial assessment, 70% of participants with respiratory diseases were classified as having oral problems. However, few subjects showed presence of dental plaque or reported problems involving the mucous membrane. The proportion of Candida-positive participants was higher in those with respiratory diseases than those with cardiovascular diseases. When comparing the Candida-positive and -negative subjects, a greater proportion of the former had problems with the lips, saliva, mucous membrane, and tongue. With regard to the time-dependent changes recorded on these problems, improvement in the condition of the lips tended to occur earlier than the conditions of the tongue. As it has been suggested that maintaining a clean tongue can be critical in patients undergoing oral intubation, it is important to continue appropriate oral health care in the acute stages.

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Necrotizing soft-tissue infections (NSTIs) are defined as infections of any of the layers within the soft tissue compartment that are associated with necrotizing changes. NSTIs are clasified into two clinical forms, gas gangrene (clostridial-, non clostridial-myonecrosis) and necrotizing fasciitis. NSTIs occurring after odontogenic infections are usually a mixed infection caused by anaerobic and aerobic bacteria. In this study, we present the case of a patient with rheumatoid arthritis under steroid treatment complicated by facial NSTIs with broad and profound necrosis of the buccal skin and subcutaneous tissues following tooth extraction.

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We recognize that delirium and deterioration of dementia were dominantly found in the patients with dementia after operation under general anesthesia. On the other hand, the patiens with maxillary and mandibular fracture sometimes have aspiration pneumonitis under the intermaxillary fixation. We experienced a good case of maxillary fracture having severe dementia treated by intramaxillary fixation with a splint instead of intermaxillary fixation. The patient, who was a 78-year-old woman, was refered to our department claiming a face blow because of the falling-down. Diagnosed maxillary fracture, the patient was set a splint in the upper jaw, and was removed it after 6 weeks-fixation. The bony healing was recognized one year after the trauma.

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Recently, Positron emission tomography-CT (PET-CT) has been widely applied to examine primary region of malignant tumor and metastasis to the lymph nodes or distant organs. And sometimes, we can find other malignancy in oral cancer by PET-CT. In this paper, we evaluated the usefulness of PETCT in screening of distant metastasis or other malignancy with oral cancer. In our study, eighteen of nintyone patients with distant metastasis or secondary malignancies were detected by PET-CT. Four were detected before operation, and fourteen were detected in follow up. It is necessary to decide treatment plan and treatment order of oral cancer with distant metastasis or other malignancy. PET-CT has an effective possibility for body screening, screening for oral cancer patients, and detecting distant metastasis or secondary malignancies.

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[in Japanese]

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