Effects of Sulfonylureas on Periodontopathic Bacteria-Induced Inflammation.

福岡歯科大学2019年

Differentiation of Apical Bud Cells in a Newly Developed Apical Bud Transplantation Model Using GFP Transgenic Mice as Donor.

Rodent mandibular incisors have a unique anatomical structure that allows teeth to grow throughout the lifetime of the rodent. This report presents a novel transplantation technique for studying the apical bud differentiation of rodent mandibular incisors. Incisal apical end tissue with green fluorescent protein from transgenic mouse was transplanted to wild type mice, and the development of the transplanted cells were immunohistologically observed for 12 weeks after the transplantation. Results indicate that the green fluorescent apical end tissue replaced the original tissue, and cells from the apical bud differentiated and extended toward the incisal edge direction. The immunostaining with podoplanin also showed that the characteristics of the green fluorescent tissue were identical to those of the original. The green fluorescent cells were only found in the labial side of the incisor up to 4 weeks. After 12 weeks, however, they were also found in the lingual side. Here the green fluorescent cementocyte-like cells were only present in the cementum close to the dentin surface. This study suggests that some of the cells that form the cellular cementum come from the apical tissue including the apical bud in rodent incisors.福岡歯科大学2015年

Glyburide inhibits the bone resorption induced by traumatic occlusion in rats.

To examine whether glyburide inhibits bone destruction caused by traumatic occlusion in a rat occlusal trauma model.Excessive mechanical stress, such as traumatic occlusion, induces expression of IL-1β and may be involved in bone resorption. NLRP3 inflammasomes have been linked to IL-1β expression, but it is currently unclear whether glyburide, the inhibiter of NLRP3 inflammasome, suppresses occlusal trauma in rats.Male SD rats aged 7 weeks were used. In the trauma group, the occlusal surface of the maxillary first right molar was raised by attaching a metal wire to apply occlusal trauma to the mandibular first right molar. In the trauma + glyburide group, the NLRP3 inhibitor glyburide was administered orally every 24 hours from 1 day before induction of occlusal trauma. Rats were euthanized after 5 or 10 days, and the maxillary first molars were harvested with the adjacent tissues for histopathological investigation. Immunohistochemical expression of IL-1β, NLRP3, and RANKL was also assessed.On day 5, bone resorption was significantly greater in the trauma group compared with the control group or the trauma + glyburide group, and there were significantly higher numbers of osteoclasts and cells positive for IL-1β, NLRP3, and RANKL in the trauma group.In this study, glyburide inhibits bone resorption by traumatic occlusion in rats. It suggests that the NLRP3/IL-1β pathway might be associated with bone resorption induced by traumatic occlusion.福岡歯科大学2019年

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers

Differentiation of Apical Bud Cells in a Newly Developed Apical Bud Transplantation Model Using GFP Transgenic Mice as Donor.

Rodent mandibular incisors have a unique anatomical structure that allows teeth to grow throughout the lifetime of the rodent. This report presents a novel transplantation technique for studying the apical bud differentiation of rodent mandibular incisors. Incisal apical end tissue with green fluorescent protein from transgenic mouse was transplanted to wild type mice, and the development of the transplanted cells were immunohistologically observed for 12 weeks after the transplantation. Results indicate that the green fluorescent apical end tissue replaced the original tissue, and cells from the apical bud differentiated and extended toward the incisal edge direction. The immunostaining with podoplanin also showed that the characteristics of the green fluorescent tissue were identical to those of the original. The green fluorescent cells were only found in the labial side of the incisor up to 4 weeks. After 12 weeks, however, they were also found in the lingual side. Here the green fluorescent cementocyte-like cells were only present in the cementum close to the dentin surface. This study suggests that some of the cells that form the cellular cementum come from the apical tissue including the apical bud in rodent incisors

Toll-like receptor 2 activation primes and upregulates osteoclastogenesis via lox-1

Abstract Background Lectin-like oxidized low-density-lipoprotein receptor 1 (Lox-1) is the receptor for oxidized low-density lipoprotein (oxLDL), a mediator in dyslipidemia. Toll-like receptor (TLR)-2 and − 4 are receptors of lipopolysaccharide (LPS) from Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Although some reports have demonstrated that periodontitis has an adverse effect on dyslipidemia, little is clear that the mechanism is explained the effects of dyslipidemia on osteoclastogenesis. We have hypothesized that osteoclast oxLDL has directly effect on osteoclasts (OCs), and therefore alveolar bone loss on periodontitis may be increased by dyslipidemia. The present study aimed to elucidate the effect of Lox-1 on osteoclastogenesis associated with TLRs in vitro. Methods Mouse bone marrow cells (BMCs) were stimulated with macrophage colony-stimulating factor into bone marrow macrophages (BMMs). The cells were also stimulated with synthetic ligands for TLR2 (Pam3CSK4) or TLR4 (Lipid A), with or without receptor activator of nuclear factor kappa-B ligand (RANKL), and assessed for osteoclastogenesis by tartrate-resistant acid phosphatase (TRAP) staining, immunostaining, western blotting, flow activated cell sorting (FACS) analysis, real-time polymerase chain reaction (PCR), and reverse transcription PCR. Results Lox-1 expression was significantly upregulated by Pam3CSK4 and Lipid A in BMCs (p < 0.05), but not in BMMs. FACS analysis identified that Pam3CSK4 upregulated RANK and Lox-1 expression in BMCs. TRAP-positive cells were not increased by stimulation with Pam3CSK4 alone, but were increased by stimulation with combination combined Pam3CSK and oxLDL. Expression of both Lox-1 and myeloid differentiation factor 88 (MyD88), an essential adaptor protein in the TLR signaling pathway, were suppressed by inhibitors of TLR2, TLR4 and mitogen-activated protein kinase (MAPK). Conclusions This study supports that osteoclastogenesis is promoted under the coexistence of oxLDL by TLR2-induced upregulation of Lox-1 in BMCs. This indicates that periodontitis could worsen with progression of dyslipidemia

A histopathologic study of the controlling role of T cells on experimental periodontitis in rats

Background/purpose: The onset and progression of periodontitis involve bacterial infection and the immune response. T cells function in the immune response and reportedly induce bone resorption in inflammatory bone loss. However, the exact role of T cells in periodontal destruction remains unclear. Using our experimental model of periodontitis, we aimed to investigate the influence of T cells on periodontal destruction. Materials and methods: Male athymic nude (Nu) and euthymic wild-type (WT) rats were divided into the immunized (I-Nu and I-WT), non-immunized (nI-Nu and nI-WT). The immunized groups were immunized intraperitoneally with lipopolysaccharide (LPS). The non-immunized groups received phosphate-buffered saline (PBS). Nothing was administered to the non-treated groups. LPS was applied to the right palatal gingival sulcus in the immunized and non-immunized groups daily for 20 days. Loss of attachment, numbers of inflammatory cells and osteoclasts, and levels of alveolar bone were investigated histopathologically and histometrically. Osteoclasts were stained with tartrate-resistant acid phosphatase. The numbers of IL-4-positive cells were evaluated immunohistologically. Results: Loss of attachment, numbers of inflammatory cells, levels of alveolar bone, and the number of osteoclasts were significantly increased in the nI-WT group compared with the nI-Nu group. However, the parameters were significantly increased in the I-Nu group compared with the I-WT group. The number of IL-4-positive cells was greater in the I-WT group than in the I-Nu group. Conclusion: T cells promote inflammation in non-immunized animals; however, they regulate these processes in immunized animals

Frozen undecalcified sagittal section of mandible 12 weeks after transplantation.

<p>The top, bottom, left, and right of each panel show the lingual, labial, incisal end, and apical end sides, respectively. (<b>A</b>) In the section stained with hematoxylin and eosin, the lingual side of the incisor presents periodontal ligament (PDL), cementum (C), dentin (D), and odontoblasts (arrowhead). The labial tissue consists of odontoblasts (arrowhead), dentin (D), enamel (E), and ameloblasts (arrow). DP, dental pulp cells. (<b>B</b>) The panel shows migration of the donor derived cells with green fluorescence. There are green fluorescent cells in the lingual side (outlined arrowheads) as well as in the labial side (arrow). (<b>C</b>) Reaction products with anti-podoplanin are observed in the nerve sheaths (asterisk), odontoblasts (arrowhead), and ameloblasts (arrow). There is a location showing cross-reaction with anti-podoplanin at the enamel matrix (double asterisk). (<b>D</b>) Merged image of <b>B</b>, <b>C</b>, and blue fluorescence of DAPI’s. Boxed area (a) in <b>D</b> indicates the identical location and size of that in <b>A</b>. (<b>E</b>, <b>F</b>) Boxed area (a) of <b>A</b> and <b>D</b> at a medium magnification. (<b>E</b>) Periodontal ligament (PDL), cementum (C), and dentin (D) are observed. (<b>F</b>) Green fluorescent cells are observed in the cementum but not in the periodontal ligament. The boxed area (b) in <b>F</b> indicates the identical location and size of that in <b>E</b>. (<b>G</b>, <b>H</b>) Boxed area (b) of <b>E</b> and <b>F</b> at a high magnification, respectively. (<b>G</b>) The HE section shows cementocyte-like cells in the cementum (C) close to the dentin (D) surface. (<b>H</b>) Green fluorescent cementocyte-like cells are observed. The nuclei are observed in the green fluorescent cells. Scale bars: 500 μm in <b>A</b>, <b>B</b>, <b>C</b>, <b>D</b>; 100 μm in <b>E</b>, <b>F</b>; 10 μm in <b>G</b>, <b>H</b>.</p