Osaka Dental University Academic Repository / 大阪歯科大学学術リポジトリ
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ムラミルジペプチド（MDP）は、ヒト歯髄線維芽細胞様細胞におけるマトリックスメタロプロテイナーゼ-3の産生を調節する
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Nucleotide-binding oligomerization domain 2, which is constitutively expressed in human dental pulp fibroblast-like cells (hDPFs), plays a role in pulpal immune responses by sensing muramyl dipeptide (MDP) from bacteria. Matrix metalloproteinase-3 (MMP-3) is abundantly expressed in acute pulpitis and acts as a mediator of the healing of dental pulp as an anti-inflammatory and regenerative factor. In the present study, we investigated the involvement of the ERK1/2 signaling pathway in MMP-3 production by MDP-stimulated hDPFs. MDP was not cytotoxic against hDPFs and did not affect their proliferation. A stimulation with MDP enhanced MMP-3 production and ERK1/2 phosphorylation. The ERK1/2 signaling pathway was involved in the production of MMP-3 by MDP-stimulated hDPFs. These results suggest that the induction of MMP-3 production by MDP-stimulated hDPFs has an anti-inflammatory function by degrading inflammatory cytokines.doctoral thesi
口腔粘膜の上皮性異形成におけるCK13, CK17, CK19, Ki 67, p53, p63, p21, p27 およびCyclin D1に関する免疫組織化学的検討
Get PDF大阪歯科大学Osaka Dental University博士（歯学）In the current World Health Organization (WHO) classification, oral epithelial dysplasia (OED) is classified using a two- or three-grade system. However, no useful auxiliary diagnostic method for determining the OED grade of specimens by this system has yet been established. In this study, specimens of not only OED, but also epithelial hyperplasia (Hp) and oral squamous cell carcinoma (OSCC) were examined immunohistochemically to investigate expression levels/rates of various antibodies. Six specimens of Hp, 13 of mild epithelial dysplasia (MiD), 11 of moderate epithelial dysplasia (MoD), 11 of severe epithelial dysplasia (SD), and 9 of OSCC obtained from the First Department of Oral and Maxillofacial Surgery at Osaka Dental University Hospital were examined immunohistochemically to determine the expression levels of CK13, CK17, CK19, Ki-67, p53, p63, p21, p27 and cyclin D1. The dysplasia grade was negatively correlated with expression of CK13 and CK17. As the dysplasia grade increased, expression rates of Ki-67, p53, p63, p21 and cyclin D1 increased, while the expression rate of p27 decreased. The expression rate of Ki-67 differed significantly between SD and OSCC, as did the expression of p53 between MoD and SD as well as between SD and OSCC. The expression rate of p63 differed significantly between MiD and MoD as well as between MoD and SD, as did the expression rate of p27 between SD and OSCC (p < 0.05). These results suggest that not only CK13, CK17, Ki-67 and p53, but also p63, p21, p27 and cyclin D1 may be linked to dysplasia. The results also suggest that calculation of Ki-67, p53, p63 and p27 expression rates could be used for OED grading and auxiliary diagnosis of OSCC.doctoral thesi
上顎洞底挙上術で使用された脱コラーゲン性ウシ骨およびコラーゲン性ブタ骨の異種移植の治癒パターン：ウサギを用いた組織学的研究
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 weeks. The loss of dimensions of the elevated area and the percentages of new bone, xenograft remnants, osteoclastic zones, vessels, inflammatory infiltrates, and soft tissues were analyzed. Three regions were evaluated: close to the bone walls (bone wall region), subjacent the sinus mucosa (submucosa region), and the center of the elevated area (middle
region). The primary variables were the percentage of new bone and xenograft remnants. Results: Between 2 and 8 weeks, the elevated areas showed a reduction of 16.3% and 52.2% in the DBBM and collagenated groups, respectively (p < 0.01 between the two areas after 8 weeks). After 8 weeks,
the highest content of new bone was observed in the bone wall region, which was higher in the collagenated group than in the DBBM group (41.6% and 28.6%, respectively; p < 0.01). A similar quantity of new bone was found between the two groups in other regions. A higher percentage of vessels in all regions evaluated (p < 0.01) and soft tissue in the sub-mucosa region (p < 0.05) was found in the collagenated group than in the DBBM group. Conclusions: The present study showed that both xenografts allowed new bone formation. In comparison with the non-collagenated xenograft, the collagenated xenograft underwent higher resorption, resulting in greater shrinkage of the elevated
space after sinus lifting and a higher content of new bone in the regions close to the bone walls. Clinical relevance: In this study, the region adjacent to the bone wall showed the highest new bone content. This region resembles the base of the sinus, closest to the sinus floor and walls, and is the most important region from a clinical point of view because it is where the implant will be installed. Residues of the biomaterial remained after 8 weeks of healing. Other reports have shown that these biomaterial residues may interfere with the integration of implants.doctoral thesi
グルコース濃度の変動が歯根膜細胞の骨芽細胞分化に及ぼす影響
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Although fluctuations in glucose concentration have been reported to regulate osteoblast differentiation, the effect on periodontal ligament cells is not clear. We investigated the effect of fluctuating glucose concentrations on the cellular functions of periodontal ligament cells (PDLCs). Variations in glucose concentration were examined in four ways: a group was incubated in 100 mg/dL glucose for 14 days; a group was incubated in 100 mg/dL glucose for 7 days, the solution was replaced with 0 mg/dL glucose, and the group was incubated for another 7 days; a group was incubated in 0 mg/dL glucose for 7 days, the solution was replaced with 100 mg/dL glucose, and the group was incubated for another 7 days; and a group was incubated in 0 mg/dL glucose for 14 days. We evaluated the osteogenic differentiation capacity by alkaline phosphatase (ALP) activity, ALP staining, calcium deposition and alizarin red staining after 14 days of culturing. We found that the osteogenic differentiation of PDLCs was enhanced in the presence of glucose, suggesting that it regulates the differentiation of PDLCs, especially in the early stage of differentiation.doctoral thesi
経鼻ダブルDNAアジュバントにより誘導されたヒト唾液タンパク特異的SIgA抗体はPorphyromonas gingivalisの付着抑制に必要である
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Background: We previously showed that fimbriae-bore from Poryphyromonas gingivalis (Pg), one of the putative periodontopathogenic bacteria specifically bound to a peptide domain (stat23, prp21) shared on statherin or acidic proline-rich protein 1 (PRP1) molecule of human salivary proteins (HSPs). Here, we investigated whether the nasal administration of DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 as double DNA adjuvant (dDA) with stat23 and prpr21 induces antigen (Ag)-specific salivary secretory IgA (SIgA) antibodies (Abs) in mice. Further, we examined that stat23- and prpr21-specific salivary SIgA Abs induced by dDA have an impact on Pg-binding to human whole saliva-coated hydroxyapatite beads (wsHAPs).
Material and methods: C57BL/6N mice were nasally immunized with dDA plus sta23 or/and prp21 peptide as Ag four times at weekly intervals. Saliva was collected one week after the final immunization and was subjected to Ag-specific ELISA. To examine the functional applicability of Ag-specific SIgA Abs, SIgA-enriched saliva samples were subjected to Pg binding inhibition assay to wsHAPs.
Results: Significantly elevated levels of salivary SIgA Ab to stat23 or prp21 were seen in mice given nasal stat23 or prp21 with dDA compared to those in mice given Ag alone. Of interest, mice nasally given the mixture of stat23 and prp21 as double Ags plus dDA, resulted in both stat23- and prp21-specific salivary SIgA Ab responses, which are mediated through significantly increased numbers of CD11c+ dendritic cell populations and markedly elevated Th1 and Th2 cytokines production by CD4+ T cells in the mucosal inductive and effector tissues. The SIgA Ab-enriched saliva showed significantly reduced numbers of live Pg cells binding to wsHAPs as compared with those in mice given double Ags without dDA or naïve mice. Additionally, saliva from IgA-deficient mice given nasal double Ags plus dDA indicated no decrease of live Pg binding to wsHAPs.
Conclusion: These findings show that HSP-derived peptides-specific salivary SIgA Abs induced by nasal administration of stat23 and prp21 peptides plus dDA, play an essential role in preventing Pg attachment and colonization on the surface of teeth, suggesting a potency that the SIgA may interrupt and mask fimbriae-binding domains in HSPs on the teeth.doctoral thesi
ラット窩洞形成下における老化細胞の局在と老化細胞除去薬による修復象牙質形成の回復
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Reparative dentin formed by dental cavity preparation (DCP) is frequently used in clinical operations and plays a pivotal role in pulp protection. Recent reports have shown that senescent cells induced by various stressors aggravate many diseases. They can be treated using senolytics, which are drugs that selectively eliminate senescent cells. However, the association between DCP, senescent cells, and senolytics remains unclear. In this study, we established a rat model of DCP and analyzed the spatiotemporal localization of senescent cells in the pulp. The results showed that p21- and p16-positive senescent cells appeared mostly around the pulp horn (PH) under DCP. Furthermore, administration of senolytics (dasatinib and quercetin) successfully eliminated these senescent cells, thereby restoring the volume of reparative dentin formation. These data indicate that senescent cells induced by DCP may hamper the formation of reparative dentin. Senescent cells may be targets for the development of new restorative dentistry therapies.doctoral thesi
歯槽骨に作製した実験的一壁性骨欠損に応用した試作サンゴ外骨格由来骨補填材による骨増生
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Bone regeneration requires cells, growth factors, and scaffolds that should have biocompatibility, porosity, and physical strength. Therefore, coral granules (CG) with diameters of 600−1000 µm were prepared as a potential graft material from cultured edaphic thermostable corals. X-ray and electron microscopy characterization revealed that CGs were porous and permeable with lumen diameters of approximately 200 µm. Human periodontal ligament fibroblasts showed significantly increased mitochondrial activity in culture seven days after adding CG. After CG filling into an experimentally created one-wall infrabony defect in a beagle dog jawbone, the defect almost completely disappeared within approximately 8 weeks, and bone tissue growth was observed in the replacement area. This could indicate extremely rapid healing of a bone defect previously considered incapable of self-healing. Based on stable supply of cultured coral (Montipora digitata), CG is potentially an ideal replacement material for alveolar and jawbone defects.doctoral thesi
顎運動モーションキャプチャを用いた咀嚼能力評価法
Get PDF大阪歯科大学Osaka Dental University博士（歯学）Background: The assessment of masticatory performance (MP) is conducted in hospitals, but is difficult to perform in nursing facilities that lack specialists in dysphagia. To determine the appropriate food form in nursing practice, a simple method of evaluating the MP should be developed.
Objective: The purpose of this study was to investigate motion parameters that influence MP by motion capture analysis of maxillofacial movement on chewing gummy jelly in healthy adults.
Methods: The subjects were 50 healthy adults. The state of chewing gummy jelly was photographed using a high-speed camera. Simultaneously, we evaluated the amount of glucose extracted (AGE) obtained with gummy jelly as a reference value for MP. The subjects were divided into two groups: normal and low masticatory groups (NG and LG, respectively) based on the AGE. The cycle of mastication was classified into 3 phases: closing phase (CP), transition phase (TP), and opening phase (OP) through motion capture analysis of the video photographed. Parameters of jaw movement, and their associations with the AGE were examined.
Results: The transition phase ratio (TR), and opening phase ratio (OR) were correlated with the AGE. Furthermore, the TR in the NG was significantly higher than in the LG, whereas the OR was significantly lower than in the LG. The age, TR, and Opening velocity were significant independent variables.
Conclusion: Motion capture technology facilitated the analysis of jaw movement. The results suggested that MP can be evaluated by analyzing the ratios of TP and OP.doctoral thesi
上顎歯列内における歯の大きさと構成
Get PDF大阪歯科大学Osaka Dental University博士（口腔科学）Purpose: To explore the relationship between tooth sizes and configurations within a single dentition, the mesiodistal and buccolingual crown diameters were measured using a dentition model, and analyzed using statistical methods.
Methods: A total of 96 maxillary dental casts were used. The mesiodistal crown diameter, buccolingual crown diameter,and crown area from the maxillary central incisor to the maxillary second molar were determined. The mean,standard deviation,median, coefficient of variation,and Spearman's rank correlation coefficients were determined. Hierarchical cluster analysis was performed to form clusters of maxillary dentitions with similar characteristics. Principal component analysis was performed to explore the characteristics of all 96 cases and each cluster. Furthermore, whether there was a difference between the clusters was asked.
Results: Maxillary lateral incisor had a large coefficient of variation and did not show a high correlation coefficient with any of the other teeth. The maxillary dentition was classified into seven groups according to the size of the configuration teeth and the size of the teeth between the tooth types. Furthermore, among the seven groups, there was a group in which the size of the teeth constituting the dentition were in harmony, and a group in which the size of one tooth or tooth type tended to increase while the size of the other tooth or tooth type tended to decrease.
Conclusion: The size of teeth in one maxillary dentition is observed within the same tooth type or between different tooth types, suggesting that they influence each other.doctoral thesi
複製老化したラット由来脱分化脂肪細胞における老化関連分泌形質
Get PDF大阪歯科大学Osaka Dental University博士（歯学）We investigated senescence in rat-derived dedifferentiated fat cells (rDFATs) with high passage numbers and analyzed the types of senescence-associated secretory phenotypes (SASPs) secreted from the rDFATs with replicative senescence. Senescent rDFATs showed a giant and flattened morphology and a low proliferative ability compared with non-senescent rDFATs. Moreover, 16 SASP-related genes (Ccl11, Ccl12, Ccl21, Ccl5, Csf2, Cxcl1, Cxcl12, Ifna2, IL11, IL12a, IL13, IL1a, IL1rn, IL6, Mif, Tnf) were significantly upregulated in the rDFATs with replicative senescence. These results indicate that DFATs also undergo cellular senescence during continuous passage cultures and may secrete various types of SASPs.doctoral thesi