Lymphangiogenesis and NOS Localization in Healing Process after Tooth Extraction in Akita Mouse.

Type I diabetes, an autoimmune disease, induces insulin deficiency, which then disrupts vascular endothelial cell function, affecting blood and lymphatic vessels. Nitric oxide (NO) is an immune-induced destructive mediator in type I diabetes, and inhibition of its production promotes arteriosclerosis. In this study, lymphangiogenesis and expression of NO synthase (NOS) during the healing process after tooth extraction were investigated immunohistochemically in control (C57BL) and Akita mice as a diabetes model. Between 1, 4, and 10 days after extraction, expression of NOS, vascular endothelial growth factor-C (VEGF-C), VEGF receptor-3 (VEGFR-3), and von Willebrand factor was strongest during the granulation tissue phase. This suggests that severe inflammation triggers regulation of NOS and these other angiogenic and lymphangiogenic factors. During the callus phase, a few days after extraction, induced osteoblasts were positive for VEGF-C and VEGFR-3 in both the control and Akita mice, suggesting that bone formation is active in this period. Bone formation in the Akita group exceeded that in the controls. Bone tissue formation was disrupted under hyperglycemic conditions, however, suggesting that such activity would be insufficient to produce new bone.

Production and physiological role of NO in the oral cavity.

Nitric oxide (NO) is a free radical which is produced from a wide variety of cells and tissues in the human body. NO is involved in the regulation of many physiological processes, such as vascular relaxation, neurotransmission, immune regulation, and cell death. NO is generated by nitric oxide synthase (NOS), which has three identified isoforms: neuronal type NOS (nNOS), endothelial type NOS (eNOS), and inducible type NOS (iNOS). Different isoforms are expressed depending on the organs, tissues, and cells, and investigation of the types and functions of enzymes expressed in various tissues is underway. The oral cavity is a space in which marked changes have been detected in NO levels, and each tissue is constantly influenced by NO. NO is a component of saliva and is produced by oral bacteria in the oral cavity and released by NOS expressed in oral mucosa. NOS isoforms expressed under normal conditions differ among the oral organs. In addition, the overexpression of NOS was involved in carcinogenesis and tumor growth progression. This review summarized the expression of NOS and functions of NO in oral cavity organs, and their roles in diseases and the influences of treatments.

Immunohistochemical localization of Nox in mouse circumvallate papillae.

Recently it has been reported that reactive oxygen species plays an important role in several physiological processes. Reactive oxygen species are generated by reactive oxygen-synthesizing enzymes (Nox). We immunohistochemically investigated expression and localization of the Nox family in a mouse circumvallate papillae. In the epithelium of the circumvallate papilla, Nox 1, 2, 3, and 4, Noxo1, and Noxa1 were expressed. In the circumvallate papilla, Nox2 was more weakly expressed in the lateral than in the upper part, and Nox3 was not expressed. In the taste buds, Nox 1, 2, 3, and 4, Noxo1, and Noxa1 were expressed; the Nox expression pattern varied with the cell type. In type II cells, Nox 1, 3, and 4, Noxo1, and Noxa1 were expressed. In type III cells, Nox2, besides Nox 1, 3, and 4, Noxo1, and Noxa1, were specifically expressed, unlike in other taste bud cells. In the mouse circumvallate papilla, Nox is always expressed, suggesting the generation of reactive oxygen species. Of note, all cells comprising taste buds expressed Nox, with each showing a specific Nox expression pattern.

Immunohistochemical localization of Nox1, Nox4 and Mn-SOD in mouse femur during endochondral ossification.

Enzymes synthesizing reactive oxygen (Nox family) have recently been identified. Elucidation of the production mechanism has been initiated, and the involvement of reactive oxygen in metabolism, intracellular transport, signal transmission and apoptosis has been reported. We immunohistochemically investigated expression and localization of the Nox family in endochondral ossification using a normal mouse femur. Weakly positive reactions with Nox1, Noxa1, and Noxo1 were observed in the zones of proliferative and prehypertrophic chondrocytes at 3 weeks of age. Nox4 was widely positive from the resting over the hypertrophic cell zone. At 18 weeks of age, none of the Nox types was expressed in chondrocytes as the zones disappeared. On the other hand, positive reactions with Nox1, Noxa1, Noxo1, and Nox4 were observed in osteoblasts in the zone of ossification at 3 weeks of age, and each Nox was also positive in osteoblasts arranged on the bone marrow side in the epiphyseal cartilage at 18 weeks of age. In addition, a reactive oxygen-eliminating enzyme, Mn-SOD, was observed only in prehypertrophic chondrocytes at 3 weeks of age, and not detected in osteoblasts. It was suggested that the Nox family is closely associated with endochondral ossification of the mouse femur, and Nox1 and Nox4 are closely involved in the chondrocyte maturation process and bone matrix formation.