Faculty Profiles - TAKASHIBA Shogo

培養ヒト歯根膜線維芽細胞における高浸透圧刺激によるsgk発現に関する研究

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/154405910508401217

明貝文夫, 妹尾京子, 山城圭介, 山本直史, 小柳津功介, 新井英雄, 西村英紀, 高柴正悟

日本歯科保存学雑誌 48 ( 6 ) 939 - 945 2005.12

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本歯科保存学会

浸透圧の上昇に応答して発現上昇するとされるsgk遺伝子が培養ヒト歯根膜線維芽細胞(HPLF)においてどのような発現動態を示すか調べるとともに,sgk発現におけるアクチン細胞骨格の関与について検討した.HPLFにおいても浸透圧の上昇に伴ってsgk発現は上昇することが明らかになり,この発現変化はアクチン細胞骨格に関係する刺激伝達系によって制御されていることが示唆された

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Isolation and Expression of FIP-2 in Wounded Pulp of the Rat Reviewed International journal

M. Oyama, F. Myokai, T. Ohira, N. Shiomi, K. Yamashiro, H. Arai, F. Nishimura, S. Takashiba

Journal of Dental Research 84 ( 9 ) 842 - 847 2005.9

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Pulpal wound healing followed by cavity preparation may involve reactionary or reparative dentinogenesis in relation to the cavity position; however, little is known about the molecular responses. We aimed to isolate and analyze genes induced or suppressed in the wounded pulp to identify molecular processes involved in the pulp responses to injury. Twenty-three cDNAs were isolated by cDNA subtraction between healthy and wounded pulp of rats. By library screening, we identified rat 14.7K-interacting protein (rFIP)-2A and B genes homologous to human FIP-2, being involved in regulating membrane trafficking and cellular morphogenesis. RT-PCR analysis showed induction for only rFIP-2B in the wounded pulp. In situ hybridization analysis revealed that both rFIP-2s were expressed strongly in condensing mesenchymal cells of the palatal process and surrounding Meckel’s cartilage, but not in intramembranous chondrogenic cells. Thus, up-regulated rFIP-2B expression may play a role in regulating membrane trafficking or cellular morphogenesis of these embryonic and wounded pulpal cells.

DOI： 10.1177/154405910508400912

Transcriptional regulation of β-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells Reviewed

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/154405910508400912

Mineshiba, J., Myokai, F., Mineshiba, F., Matsuura, K., Nishimura, F., Takashiba, S.

FEMS Immunology and Medical Microbiology 45 ( 1 ) 37 - 44 2005.7

Periodontal Treatment in Severe Aplastic Anemia Reviewed International journal

Kosuke Oyaizu, Fumi Mineshiba, Junji Mineshiba, Hirokazu Takaya, Fusanori Nishimura, Ichiro Tanimoto, Hideo Arai, Shogo Takashiba

Journal of Periodontology 76 ( 7 ) 1211 - 1216 2005.7

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Background: Aplastic anemia (AA) is a rare hematologic disease characterized by hypo-cellular bone marrow. The clinical features include fatigue, increased bruising, and gingival bleeding caused by anemia, leukopenia, and thrombocytopenia. A patient with AA is at high risk for infection because of leukopenia. The risk of systemic infection is especially high in AA patients with severe local infections, including periodontitis. Accordingly, periodontal treatment should include antibiotic prophylaxis to reduce the risk of systemic infection. However, treatment of periodontitis in the AA patient is significantly complicated by the bleeding disorder. We present a case report of the successful periodontal treatment of an AA patient with spontaneous gingival bleeding.
Methods: The patient was closely monitored for platelet and neutrophil counts before every treatment. The patient's platelet count was always under 10,000/mu l. Therefore, it was necessary to increase platelet counts to over 25,000/mu l by transfusion, after which subgingival scaling with anesthesia was performed. When the neutrophil count was less than 2,000/mu l, local minocycline chemotherapy was applied to the pockets. Periodontal infection was monitored by detection of bacterial DNA and measurement of serum immunoglobulin (Ig) G titer against periodontal bacteria.
Results: Following the physical and chemical treatment, the gingival appearance improved dramatically and the spontaneous gingival bleeding disappeared. Moreover, the IgG titer against periodontal bacteria decreased to normal range and specific periodontal pathogens were no longer detectable in the tested pockets.
Conclusion: We believe that the treatment strategy in the present report provides new sight into treatment planning for severely medically compromised patients.

DOI： 10.1902/jop.2005.76.7.1211

Role of helper T cells in the humoral immune responses against 53-kDa outer membrane protein from Porphyromonas gingivalis Reviewed

Kato, N, Ohyama, H, Nishimura, F, Matsushita, S, Takashiba, S, Murayama, Y

Oral Microbiology and Immunology 20 ( 2 ) 112 - 117 2005.4

Thiazolidinedione (Pioglitazone) Blocks P. gingivalis- and F. nucleatum, but not E. coli, Lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) Production in Adipocytes Reviewed International journal

M. Yamaguchi, F. Nishimura, H. Naruishi, Y. Soga, S. Kokeguchi, S. Takashiba

Journal of Dental Research 84 ( 3 ) 240 - 244 2005.3

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

An elevated level of C-reactive protein (CRP) predicts the future development of coronary heart disease. Periodontitis appears to up-regulate CRP. CRP is produced by hepatocytes in response to interleukin-6 (IL-6). A major source of IL-6 in obese subjects is adipocytes. We hypothesized that lipopolysaccharide (LPS) from periodontal pathogens stimulated adipocytes to produce IL-6, and that the production was suppressed by the drugs targeted against insulin resistance, thiazolidinedione (pioglitazone), since this agent potentially showed an anti-inflammatory effect. Mouse 3T3-L1 adipocytes were stimulated with E. coli, P. gingivalis, and F. nucleatum LPS. The IL-6 concentration in culture supernatants was measured. All LPS stimulated adipocytes to produce IL-6. Although pioglitazone changed adipocyte appearance from large to small, and completely suppressed P. gingivalis and F. nucleatum LPS-induced IL-6 production, E. coli LPS-induced IL-6 production was not efficiently blocked. Thus, pioglitazone completely blocked periodontal-bacteria-derived LPS-induced IL-6 production in adipocytes, a major inducer of CRP.

DOI： 10.1177/154405910508400306

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/154405910508400306

Long-term cyclosporin A exposure suppresses cathepsin-B and -L activity in gingival fibroblasts. Reviewed International journal

Mayumi Yamaguchi, Koji Naruishi, Hisa Yamada-Naruishi, Kazuhiro Omori, Fusanori Nishimura, Shogo Takashiba

Journal of periodontal research 39 ( 5 ) 320 - 6 2004.10

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

BACKGROUND: Gingival overgrowth is a common side-effect following administration of cyclosporin A. We reported previously that lysosomal protease cathepsin-L activity, but not cathepsin-B, was significantly suppressed by short-term cyclosporin A exposure in human gingival fibroblasts. Although this suppression may lead to decreased degradation of gingival connective tissue, a net increase in matrix proteins, and gingival overgrowth, the effects of cyclosporin A need to be more elucidated, considering the long-term use for patients following organ transplantation. OBJECTIVE: The aim of the present study was to evaluate the effects of clinically relevant doses of cyclosporin A on cultured human gingival fibroblasts. We evaluated the effects of long-term cyclosporin A exposure on cell proliferation, mRNA expression of various proteases and both cathepsin-B and -L activity in human gingival fibroblasts. MATERIALS AND METHODS: Human gingival fibroblasts were isolated from three donors' healthy gingiva and cultured from five to eight passages with or without 200 ng/ml of cyclosporin A. Proliferative activity of cyclosporin A-treated cells was examined using MTT assay. Total RNA and cellular proteins were collected for semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and for measurement of the cathepsin-B and -L activity. RESULTS: Long-term cyclosporin A exposure had no effects on cell proliferation. Accumulation of cathepsin-B, -H and -L mRNA was markedly suppressed by long-term cyclosporin A exposure, whereas accumulation of another lysosomal enzyme N-acetyl-beta-D-glucosaminidase mRNA, which is involved in remodeling of gingival epithelium, was not apparently impaired in cyclosporin A-treated cells. Accumulation of matrix metalloprotease-1 (MMP-1) and tissue inhibitor of matrix metalloprotease-1 (TIMP-1) mRNA, which are involved in remodeling of extracellular matrix, also was not impaired. In addition, we demonstrated that long-term cyclosporin A exposure significantly suppressed not only the activity of the active form of cathepsin-(B + L) compared to the activity in non-treated cells (p = 0.0458), but also the activity of the active form of cathepsin-B (p < 0.0001) in human gingival fibroblasts. CONCLUSION: The decreased ability of protein degradation by not only cathepsin-L but also cathepsin-B is, at least, one of the several factors developing the cyclosporin A-induced gingival overgrowth.

DOI： 10.1111/j.1600-0765.2004.00746.x

Identification of Genes Differentially Regulated in Rat Alveolar Bone Wound Healing by Subtractive Hybridization Reviewed International journal

T. Ohira, F. Myokai, N. Shiomi, K. Yamashiro, T. Yamamoto, Y. Murayama, H. Arai, F. Nishimura, S. Takashiba

Journal of Dental Research 83 ( 7 ) 546 - 551 2004.7

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-α-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase l3 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

DOI： 10.1177/154405910408300707

High glucose enhances interleukin-6-induced vascular endothelial growth factor 165 expression via activation of Gp130-mediated p44/42 MAPK-CCAAT/enhancer binding protein signaling in gingival fibroblasts Reviewed

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/154405910408300707

Omori, K, Naruishi, K, Nishimura, F, Yamada-Naruishi, H, Takashiba, S

Journal of Biological Chemistry 279 ( 8 ) 6643 - 6649 2004.2

Systemic up-regulation of sTNFR2 and IL-6 in Porphyromonas gingivalis pneumonia in mice Reviewed

Petelin, M, Naruishi, K, Shiomi, N, Mineshiba, J, Arai, H, Nishimura, F, Takashiba, S, Murayama, Y

Experimental and Molecular Pathology 76 ( 1 ) 76 - 81 2004.2

セメント質及び歯根膜の感染が疑われた歯の意図的再植が成功した1例 Reviewed

山崎太士, 河野隆幸, 清水明美, 明貝文夫, 新井英雄, 西村英紀, 村山洋二, 高柴正悟

日本歯科保存学雑誌 47 ( 1 ) 31 - 36 2004.2

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本歯科保存学会

16歳(再植施行時)女.歯科矯正治療に際して発見された下顎左側第一大臼歯根尖周囲のX線透過病変の精査加療で受診した.X線写真から,近心根および遠心根根尖付近の穿孔部は,再封鎖された状態であった.根管充填によっていったんは治癒傾向を示したものの,根尖部が嚢胞腔内に長期問さらされることによって生じた感染セメント質を原因とする下顎左側第一大臼歯歯根嚢胞と診断した.感染セメント質の除去と,根尖部の再封鎖を目的とした意図的再植を計画した.自覚的および他覚的症状はなく,機能的にも問題なく経過した

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CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects Reviewed

Soga, Y., Nishimura, F., Ohtsuka, Y., Araki, H., Iwamoto, Y., Naruishi, H., Shiomi, N., Kobayashi, Y., Takashiba, S., Shimizu, K., Gomita, Y., Oka, E.

Life Sciences 74 ( 7 ) 827 - 834 2004.1

歯周病と全身疾患歯周病の病態から Invited Reviewed

村山洋二, 西村英紀, 岩本義博, 高柴正悟

日本歯周病学会会誌 45 ( 4 ) 325 - 348 2003.12

Authorship：Last author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本歯周病学会

歯周病は顕著なグラム陰性菌によって引き起こされる細菌感染性の疾患であるが,その病態は局所の宿主反応によって規定されている.したがって,歯根面のバイオフィルムだけでなく歯周炎局所の炎症反応を修飾・調整している仲介分子が,糖尿病,心臓冠動脈疾患,低体重児出産,呼吸器疾患などの全身疾患症状のマイナス要因とみなされるのである.このように歯周病は健康と福祉の必須要因として認識されつつある.そこで,生活習慣病の観点に立って,1)歯周病の病態・病因,2)歯周炎と全身疾患の関わり,3)歯周病における保健の意義について述べた

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世界の歯周病学の潮流と私たち Invited Reviewed

高柴正悟

岡山歯学会雑誌 22 ( 2 ) 253 - 266 2003.12

c-jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)-6-induced vascular endothelial growth factor (VEGF) production: Cyclosporine a partially mimics this inhibitory effect Reviewed

Naruishi, K., Nishimura, F., Yamada-Naruishi, H., Omori, K., Yamaguchi, M., Takashiba, S.

Transplantation 76 ( 9 ) 1380 - 1382 2003.11

Application of denaturing gradient gel electrophoresis (DGGE) to the analysis of microbial communities of subgingival plaque Reviewed

Fujimoto, C, Maeda, H, Kokeguchi, S, Takashiba, S, Nishmura, F, Arai, H, Fukui, K, Murayama, Y

Journal of Periodontal Research 38 ( 4 ) 440 - 445 2003.8

Gene profiling in human periodontal ligament fibroblasts by subtractive hybridization Reviewed

Yamamoto, T, Myokai, F, Nishimura, F, Ohira, T, Shiomi, N, Yamashiro, K, Arai, H, Murayama, Y, Takashiba, S

Journal of Dental Research 82 ( 8 ) 641 - 645 2003.8

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Genes expressed by human periodontal ligament fibroblasts (HPFs) are likely to be associated with specific functions of the ligament. The aim of this study is to profile genes expressed highly by HPFs. A library (6 × 10³pfu) was constructed, followed by subtraction of HPF cDNAs with human gingival fibroblast (HGF) cDNAs. Reverse-dot hybridization revealed that 33 clones expressed higher levels of specific mRNAs in HPFs than in HGFs. These were mRNAs for known genes, including several associated with maturation and differentiation of cells. None had been reported in PFs. One clone, PDL-29, identified as a COX assembly factor, showed much stronger mRNA expression in HPFs than in HGFs in culture. In rat periodontium, however, PDL-29 mRNA expression was similar in PFs and GFs. These results suggest that HPFs express many previously unreported genes associated with maturation and differentiation, but expression can differ in vitro and in vivo.

DOI： 10.1177/154405910308200814

Antimicrobial periodontal treatment decreases serum C-reactive protein, tumor necrosis factor-alpha, but not adiponectin levels in patients with chronic periodontitis Reviewed

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/154405910308200814

Iwamoto, Y, Nishimura, F, Soga, Y, Takeuchi, K, Kurihara, M, Takashiba, S, Murayama, Y

Journal of Periodontology 74 ( 8 ) 1231 - 1236 2003.8

Tumor necrosis factor-alpha gene (TNF-α) −1031/−863, −857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese Reviewed International journal

Yoshihiko Soga, Fusanori Nishimura, Hideki Ohyama, Hiroshi Maeda, Shogo Takashiba, Yoji Murayama

Journal of Clinical Periodontology 30 ( 6 ) 524 - 531 2003.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Objectives: Tumour necrosis factor-alpha (TNF-alpha ) and interleukin-1beta (IL-1beta ) participate in the establishment of inflammatory lesions in periodontitis. High production of these cytokines may relate to the severity of periodontitis. There have already been several studies examining the association between periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine productivity. Recently, new SNPs of TNF-alpha , -1031, -863 and -857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high TNF-alpha production. For a better understanding of the genetic factors associated with the severity of periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on TNF-alpha or IL-1beta SNPs associated with periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe periodontitis in Japanese and the following SNPs: five in the TNF-alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta gene (-511, -31, +3953).
Material and Methods: A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe adult periodontitis and 64 healthy subjects. TNF-alpha and IL-1beta SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism for all subjects. TNF-alpha and IL-1beta production from LPS-stimulated monocytes/macrophages was also measured for 15 healthy male subjects.
Results: TNF-alpha production in TNF-alpha -1031/-863 (linkage disequilibrated) or -857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF-alpha -1031, -863 or -857 SNPs among severe periodontitis patients was significantly higher than in healthy subjects.
Conclusion: Since the frequency of subjects who carried at least one variant allele in TNF-alpha -1031, -863 or -857 SNPs was higher in periodontitis patients than in healthy subjects, TNF-alpha -1031, -863 and -857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

DOI： 10.1034/j.1600-051x.2003.00287.x