多形腺腫における細胞分化の促進因子としての Wnt シグナルの可能性

There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the ‘mixed’ differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.2014博士（歯学）松本歯科大

エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化

The expression of HSP27 and some CKs were examined the 40 cases of typical solid/multicystic ameloblastoma using immunohistochemical techniques. In order to examine the relevance of HSP in cell differentiation, we focused on the cytoskeletal expression of CK. CK19 is a marker of typical odontogenic epithelium widely observed in follicular and plexiform types of ameloblastomas. Since staining with CK14 is one of the measures of the differentiation potential of squamous cells and is extensively expressed in both follicular and plexiform types, it implies that squamous differentiation of each type can occur. CK8 was strongly detected in tumor nests in plexiform type but weakly detected in follicular type. It was considered that the expression of HSP27 in plexiform type correlated with the expression of CK8 suggesting that HSP27 might have regulated the expression of CK8.2013博士（歯学）松本歯科大

Notch signaling acts on cell differentiation and acquisition of tumor-specific character of oral neoplasms

Histopathological findings of oral neoplasm cell differentiation and metaplasia suggest that tumor cells induce their own dedifferentiation and re-differentiation and may lead to the formation of tumor-specific histological features. Notch signaling is involved in the maintenance of tissue stem cell nature and regulation of differentiation and is responsible for the cytological regulation of cell fate, morphogenesis, and/or development. In our previous study, immunohistochemistry was used to examine Notch expression using cases of odontogenic tumors and pleomorphic adenoma as oral neoplasms. According to our results, Notch signaling was specifically associated with tumor cell differentiation and metaplastic cells of developmental tissues. Notch signaling was involved in the differentiation of the ductal epithelial cells of salivary gland tumors and ameloblast-like cells of odontogenic tumors. However, Notch signaling was also involved in squamous metaplasia, irrespective of the type of developmental tissue. In odontogenic tumors, Notch signaling was involved in epithelial–mesenchymal interactions and may be related to tumor development and tumorigenesis. This signaling may also be associated with the malignant transformation of ameloblastomas. Overall, Notch signaling appears to play a major role in the formation of the characteristic cellular composition and histological features of oral neoplasms, and this involvement has been reviewed here

Recent Developments of Functional Scaffolds for Craniomaxillofacial Bone Tissue Engineering Applications

Autogenous bone grafting remains a gold standard for the reconstruction critical-sized bone defects in the craniomaxillofacial region. Nevertheless, this graft procedure has several disadvantages such as restricted availability, donor-site morbidity, and limitations in regard to fully restoring the complicated three-dimensional structures in the craniomaxillofacial bone. The ultimate goal of craniomaxillofacial bone reconstruction is the regeneration of the physiological bone that simultaneously fulfills both morphological and functional restorations. Developments of tissue engineering in the last two decades have brought such a goal closer to reality. In bone tissue engineering, the scaffolds are fundamental, elemental and mesenchymal stem cells/osteoprogenitor cells and bioactive factors. A variety of scaffolds have been developed and used as spacemakers, biodegradable bone substitutes for transplanting to the new bone, matrices of drug delivery system, or supporting structures enhancing adhesion, proliferation, and matrix production of seeded cells according to the circumstances of the bone defects. However, scaffolds to be clinically completely satisfied have not been developed yet. Development of more functional scaffolds is required to be applied widely to cranio-maxillofacial bone defects. This paper reviews recent trends of scaffolds for crania-maxillofacial bone tissue engineering, including our studies

Vacuum Ultraviolet (VUV) Light Photofunctionalization to Induce Human Oral Fibroblast Transmigration on Zirconia.

Soft tissue adhesion and sealing around dental and maxillofacial implants, related prosthetic components, and crowns are a clinical imperative to prevent adverse outcomes of periodontitis and periimplantitis. Zirconia is often used to fabricate implant components and crowns. Here, we hypothesized that UV treatment of zirconia would induce unique behaviors in fibroblasts that favor the establishment of a soft tissue seal. Human oral fibroblasts were cultured on zirconia specimens to confluency before placing a second zirconia specimen (either untreated or treated with one minute of 172 nm vacuum UV (VUV) light) next to the first specimen separated by a gap of 150 µm. After seven days of culture, fibroblasts only transmigrated onto VUV-treated zirconia, forming a 2.36 mm volume zone and 5.30 mm leading edge. Cells migrating on VUV-treated zirconia were enlarged, with robust formation of multidirectional cytoplastic projections, even on day seven. Fibroblasts were also cultured on horizontally placed and 45° and 60° tilted zirconia specimens, with the latter configurations compromising initial attachment and proliferation. However, VUV treatment of zirconia mitigated the negative impact of tilting, with higher tilt angles increasing the difference in cellular behavior between control and VUV-treated specimens. Fibroblast size, perimeter, and diameter on day seven were greater than on day one exclusively on VUV-treated zirconia. VUV treatment reduced surface elemental carbon and induced superhydrophilicity, confirming the removal of the hydrocarbon pellicle. Similar effects of VUV treatment were observed on glazed zirconia specimens with silica surfaces. One-minute VUV photofunctionalization of zirconia and silica therefore promotes human oral fibroblast attachment and proliferation, especially under challenging culture conditions, and induces specimen-to-specimen transmigration and sustainable photofunctionalization for at least seven days

Melanoma Inhibitory Activity and Melanoma Inhibitory Activity 2 as Novel Immunohistochemical Markers of Oral Epithelial Dysplasia

Oral potentially malignant disorders are associated with the development of oral squamous cell carcinoma (OSCC). Most OSCCs are diagnosed via histopathology as oral epithelial dysplasia (OED), but the histologic diagnostic criteria remain non-uniform. Accordingly, the establishment of a diagnostic marker to assist in diagnosis could contribute towards cancer prevention. Melanoma inhibitory activity (MIA) and MIA2 are involved in tumor growth, invasion, and lymph node metastasis in various malignancies. The purpose of this study was to clarify the usefulness of MIA and MIA2 as diagnostic markers of oral mucosal lesions. The expression of MIA and MIA2 was analyzed immunohistochemically in 100 specimens (10 specimens with normal oral mucosa (NOM) and 30 specimens each with low-grade epithelial dysplasia (LED), high-grade epithelial dysplasia (HED), and OSCC). Immunohistochemical results were evaluated based on the Allred scoring system. Cytoplasmic expression of MIA and MIA2 increased in the order of LED, HED, and OSCC. All NOM specimens were negative for cytoplasmic expression. Significant differences were observed between the groups (NOM vs. HED, p < 0.05, NOM vs. OSCC, p < 0.001). These results demonstrate that MIA and MIA2 are expressed in the oral mucosa within early neoplastic lesions and suggest that MIA and MIA2 are useful novel immunohistochemical markers for discriminating between normal tissue and OED