Retrospective study on the effect of adipose stem cell transplantation on jaw bone regeneration.

PURPOSE: In patients with jaw bone atrophy, dental implant therapy requires bone augmentation on the alveolar ridge. Common methods are autologous bone transplantation or bone substitutes. The latter technique is less surgically invasive because it does not require bone harvesting; however, blood supply from the surrounding tissues and local differentiation of osteoblasts are not guaranteed, so adequate bone regeneration for dental implant therapy is often not achieved. Therefore, at our hospital we introduced a bone regenerative medicine technique that uses adipose stem cells (ASCs) from adipose tissue. The new approach is less surgically invasive and appears to have a better effect on bone regeneration. The current retrospective study aimed to demonstrate the efficacy of ASC transplantation in patients who underwent alveolar ridge bone augmentation at our hospital. METHODS: We compared medical records, postoperative radiographic findings, and histological results from patients treated between January 2018 and March 2022 by augmentation of the jaw bone with bone substitutes (carbonate apatite) mixed with ASCs (ASCs+ group) and those treated with bone substitutes (carbonate apatite) alone (ASCs- group). RESULTS: After 6 months, the survival rate of augmented bone and the gray scale value in dental cone beam computed tomography (a bone density index) were significantly higher in the ASCs+ group than in the ASCs- group. Histological analysis at 6 months showed more adequate bone tissue regeneration in the ASCs+ group. CONCLUSIONS: The findings suggest the effectiveness of using ASCs in bone augmentation on the alveolar ridge in patients with jaw bone atrophy.

Study on internal structure of zygomatic bone using micro-finite element analysis model--differences between dentulous and edentulous dentition in Japanese cadavers.

The purpose of this study was to analyze changes in the internal structure of zygomatic bone using a micro-finite element analysis model (muFEA) and compare angular orientation of trabeculae against compressive force in edentulous and dentulous jaws. Twenty zygomatic bones from dentulous jaws and 20 zygomatic bones from edentulous jaws harvested from Japanese male cadavers were used. From 2-dimensional slice images, we reconstructed 3-dimensional (3D) structure by the volume rendering method using micro-computed tomography (micro-CT). To analyze mechanical properties, all voxels were converted to muFEA models. The angle between the strongest direction of trabecular bone and the axial loading direction (angle alpha) was then determined using the muFEA models. In the 3-D reconstruction images, trabecular density in dentulous jaws was higher than that in edentulous jaws at all loci. Trabeculae in dentulous jaws showed a plate-like structure. The muFEA modeling revealed that the angle of the trabeculae at the Jugale in edentulous jaws was lower than that in dentulous jaws. This suggests that the internal structure of trabeculae is influenced by occlusal force in zygomatic bone from edentulous jaws.

Effect of cevimeline on radiation-induced salivary gland dysfunction and AQP5 in submandibular gland in mice.

The aim of this study was to clarify the effects of the muscarinic receptor agonist, cevimeline, on saliva flow and expression of aquaporin5 (AQP5) in submandibular gland after X-ray irradiation. Using a previously established radiation-induced xerostomia model mouse, saliva flow from at 7 days before irradiation to at 28 days after irradiation was investigated in mice that were treated with cevimeline before or after irradiation. Radiation caused a significant decrease in saliva flow compared with nonirradiated salivary glands. Cevimeline post-treatment also caused a significant decrease in saliva flow. In contrast, cevimeline pre-treatment did not significantly decrease saliva flow. Expression of AQP5 fluorescent intensity and mRNA were also analyzed. Irradiation significantly decreased expression of AQP5 in submandibular gland. However, pre-treatment with cevimeline prevented this decrease in AQP5 expression. These data suggest that pretreatment with cevimeline prevents radiation-induced xerostomia and radiation-induced decrease in expression of AQP5 in submandibular gland.

Peroxynitrite formation in radiation-induced salivary gland dysfunction in mice.

Xerostomia frequently arises in patients with head and neck malignancies that are treated by radiation. However, the mechanisms responsible for the destruction of the salivary gland remain unknown. We previously established a xerostomia model of mice and identified the pathway through which nitric oxide (NO) affects the pathogenesis of radiation-induced salivary gland dysfunction. Although the toxicity of NO alone is modest, NO with superoxide anion (O2(*-)) rapidly forms peroxynitrite (ONOO), a more powerful toxic oxidant. In this study, we used the experimental model to examine: 1) when NO and O2(*-) production is maximum in the salivary gland after irradiation;2) whether peroxynitrite, as assessed by nitrotyrosine production, is responsible for salivary gland dysfunction; and 3) the effect of the iNOS selective inhibitor, aminoguanidine (AG), on nitrotyrosine formation. The increases in production of NO and O2(*-) in the salivary gland peaked on day 7 after irradiation. Nitrotyrosine detected immunohistochemically was significantly reduced by AG in the salivary gland. On the basis of these results, we concluded that NO together with O2(*-) forms the more reactive ONOO, which might be an important pathogenic factor in radiation-induced salivary gland dysfunction.

Internal structure of zygomatic bone related to zygomatic fixture.

PURPOSE: The purposes of this study were to investigate the internal structure of the edentulous zygomatic bone, which provides anchorage for the zygomatic fixture, using micro-computed tomography, and to examine the relation between the internal structure of the edentulous zygomatic bone and the zygomaticus fixture. MATERIALS AND METHODS: Twenty-eight zygomatic bones of edentulous maxillae from cadavers were used. The mean age of cadaver specimens was 79.6 years. The specimens were analyzed using micro-computed tomography. RESULTS: The internal structure of edentulous maxillae had thicker trabeculae in the region at the tip of the zygomaticus fixture than in other regions. CONCLUSIONS: The present findings suggest that the presence of wider and thicker trabeculae at the end of the fixture promotes initial fixation. Also, when the trabeculae are able to support occlusal force after successful osseointegration, this thickening greatly aids the support of the fixture at the tip of the fixture, where stress is thought to be concentrated. In addition, the occlusal force was applied to the entire zygomatic bone. This preliminary study suggests that better understanding of the internal structure of the zygomatic bone will provide further information about the direction of installation of the zygomatic fixture, the ideal position of the zygomatic fixture, and the prognosis of implant therapy.

Activation of Epstein-Barr virus by saliva from Sjogren's syndrome patients.

The aim of this study was to examine the mechanism of Epstein-Barr virus (EBV) activation by soluble factors from the inflamed salivary glands of patients with Sjogren's syndrome (SS). Saliva from SS patients was used to examine the regulation of EBV activation by an inflammatory salivary microenvironment. Transient transfection of the EBV-negative salivary gland cell line (HSY) with BZLF1, a trans-activating EBV gene promoter-fusion construct (Zp-luc), was used in this study. The results showed that under conditions where the BZLF1 promoter is activated by potent stimuli, SS saliva (from eight of 12 patients) exerts a significant effect on expression of the luciferase gene. A specific inhibitor of protein kinase C did not affect the SS saliva-induced Zp-luc activity, whereas treatment with inhibitors of calmodulin, calcineurin and IP3, dose-dependently decreased this induction. Transforming growth factor beta1 (TGF-beta1), which is known to be expressed in SS salivary glands, dose-dependently induced Zp-luc activity. Hence, these results demonstrate the activation of EBV by SS saliva and suggest that EBV activation at the inflammatory site may occur in the presence of TGF-beta1 via triggering of the mitogen-activated protein kinase (MAPK) kinase signalling pathway.

Possible role of nitric oxide in radiation-induced salivary gland dysfunction.

In this study, we developed a murine model of xerostomia to elucidate the mechanism of radiation-induced salivary gland dysfunction and determined the levels of nitric oxide (NO) in the salivary glands to assess its involvement in the salivary dysfunction induced by radiation. In addition, an inhibitor of NO synthesis was administered to the model in vivo, and its effect on saliva secretion was investigated. Salivary gland irradiation at a dose of 15 Gy caused a significant decrease in secretion compared to unirradiated salivary glands. There were no marked differences between the irradiated mice and unirradiated mice in water or food consumption or in body weight changes. The NO levels in the cultured salivary gland epithelial cells were increased by treatment with a combination of interferon gamma (Ifng), interleukin 1-beta (Il1b), and tumor necrosis factor alpha (Tnfa). Irradiation increased the NO level in the salivary gland tissue. The presence of N(G)-monomethyl-l-arginine acetate (l-NMMA), an inhibitor of NO synthesis, caused a decrease in the NO level in cultured salivary gland tissues after irradiation. Administration of l-NMMA to irradiated mice improved saliva secretion. These results suggest that excessive production of NO induced by radiation is involved in the formation of radiation-induced xerostomia. The finding that administration of an inhibitor of NO synthesis ameliorated the dysfunction of irradiated salivary glands indicates that NO plays a role as a mediator of the dry mouth symptoms that occur after irradiation.