Shogo Takashiba

Okayama University, Okayama, Okayama, Japan

Are you Shogo Takashiba?

Claim your profile

Publications (177)376.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multi-center, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4- and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval, CI 32.7502-41.5123, n = 208) than it was in the placebo group at 21.579% (95%CI 16.3571-26.8011, n = 100, p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multi-center, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6- and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks was 1.927 mm (95%CI 1.6615-2.1920, n = 108) in the rhFGF-2 group and 1.359 mm (95%CI 1.0683-1.6495, n = 109) in the EMD group, showing non-inferiority (a pre-specified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in both studies. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony defect, and its efficacy was superior in rhFGF-2 compared to EMD treatments. This article is protected by copyright. All rights reserved.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2015; DOI:10.1002/jbmr.2738 · 6.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objective The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites.Material and Methods This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4–6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid.ResultsThe levels of IL-1β, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1β increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5–6 mm. In the test group, IL-1β decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1β, IL-6 and TNF-α were closely correlated with each other.Conclusion This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.
    Journal of Periodontal Research 08/2015; DOI:10.1111/jre.12311 · 2.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aggressive periodontitis is a great challenge to clinicians when providing orthodontic treatment because of the potential for progression of periodontal disease. In this article, we report the successful comprehensive orthodontic treatment of bimaxillary protrusion and severe crowding in an adult with generalized aggressive periodontitis. A woman, aged 22 years 7 months, with a chief complaint of incisal crowding was diagnosed with a skeletal Class I malocclusion associated with severe anterior crowding, possibly worsened by generalized aggressive periodontitis. In addition to a periodontal examination, a blood IgG antibody titer analysis and microbiologic examination for periodontal pathogens were used to diagnose the type of periodontal disease and determine the proper timing to initiate orthodontic treatment. The total active treatment period was 28 months, followed by periodontal prostheses and regeneration therapy. Consequently, satisfactory facial profile, occlusion, and periodontal health were maintained for at least 36 months. These results indicate that efficient screening is important for providing successful orthodontic treatment in patients with advanced periodontal disease. This report also demonstrates the diagnostic importance of blood IgG antibody titer assays and microbiologic examinations to detect periodontal pathogens. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.
    American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 06/2015; 147(6). DOI:10.1016/j.ajodo.2014.09.022 · 1.38 Impact Factor
  • Koji Naruishi · Akiko Kunita · Toshihiko Nagata · Shogo Takashiba · Seiji Adachi ·

    Geriatrics & Gerontology International 05/2015; 15(5). DOI:10.1111/ggi.12430 · 2.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The number of elderly inpatients has been steadily increasing worldwide. However, the ability to predict the degree of improvement of functional capacity after comprehensive examination of elderly inpatients is still lacking. The purpose of this study was to investigate the predictors of improved functional outcome after rehabilitation of elderly inpatients. We performed a retrospective cohort study with 1,079 patients (age <70 years: N=331, age ≥70 years: N=748) who had been admitted to Tottori Municipal Hospital. Functional Independence Measure (FIM) scores were measured both at admission and discharge to calculate FIM gain and efficiency. Of these patients, 262 patients had oral examinations on admission. The Mann-Whitney U-test or chi-square test was used for statistical analyses. Conditional logistic regression analysis was used to compute the odds ratio (OR) and 95% confidence interval (CI). Cut-off values of FIM scores to determine if elderly inpatients were able to return home after discharge were determined using a receiver operating characteristic curve. FIM scores, including FIM gain and efficiency, of elderly patients were significantly lower than those of middle-aged patients. Inability to close the lips and dysfunctional tongue movement, but not the loss of teeth, were correlated with a reduced improvement of FIM scores. Cognitive impairment and aspiration pneumonia, but not cerebrovascular disease, were also correlated with a reduced improvement of FIM scores. Interestingly, FIM scores were significantly lower in patients with both cerebrovascular disease and a loss of posterior occlusion. Factors shown to have a significant impact on the improvement of FIM scores included the stable posterior occlusion (OR: 2.23, 95% CI: 1.2-4.1), closed lips (OR: 5.15, 95% CI: 2.3-11.7), functional tongue movement (OR: 5.74, 95% CI: 3.0-11.0), presence of cognitive impairment (OR: 0.31, 95% CI: 0.17-0.49), and presence of aspiration pneumonia (OR: 0.27, 95% CI: 0.15-0.51). Age and disorder of oral function may be significant predictors of improved functional capacity after rehabilitation for elderly inpatients.
    Clinical Interventions in Aging 12/2014; 9:2133-41. DOI:10.2147/CIA.S73388 · 2.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The periodontal ligament is a multifunctional soft connective tissue, which functions not only as a cushion supporting the teeth against occlusal force, but is also a source of osteogenic cells that can regenerate neighboring hard tissues. Periodontal ligament cells (PDL cells) contain heterogeneous cell populations, including osteogenic cell progenitors. However, the precise mechanism underlying the differentiation process remains elusive. Cell differentiation is regulated by the local biochemical and mechanical microenvironment that can modulate gene expression and cell morphology by altering actin cytoskeletal organization mediated by Rho-associated, coiled-coil containing protein kinase (ROCK). To determine its role in PDL cell differentiation, we examined the effects of ROCK on cytoskeletal changes and kinetics of gene expression during osteogenic differentiation. PDL cells were isolated from human periodontal ligament on extracted teeth and cultured in osteogenic medium for 14 days. Y-27632 was used for ROCK inhibition assay. Osteogenic phenotype was determined by monitoring alkaline phosphatase (ALP) activity and calcium deposition by Alizarin Red staining. ROCK-induced cytoskeletal changes were examined by immunofluorescence analysis of F-actin and myosin light chain 2 (MLC2) expression. Real-time PCR was performed to examine the kinetics of osteogenic gene expression. F-actin and phospho-MLC2 were markedly induced during osteogenic differentiation, which coincided with upregulation of ALP activity and mineralization. Subsequent inhibition assay indicated that Y-27632 significantly inhibited F-actin and phospho-MLC2 expression in a dose-dependent manner with concomitant partial reversal of the PDL cell osteogenic phenotype. PCR array analysis of osteogenic gene expression indicated that extracellular matrix genes, such as fibronectin 1, collagen type I and III, and biglycan, were significantly downregulated by Y27632. These findings indicated crucial effects of ROCK in cytoskeletal reorganization and differentiation of PDL cells toward osteogenic cells. ROCK contributes to induction of osteogenic differentiation by synergistic increases in extracellular matrix gene expression in PDL cells.
    Differentiation 09/2014; 88(2-3). DOI:10.1016/j.diff.2014.09.002 · 3.44 Impact Factor

  • Supportive Care Cancer 09/2014; 22(12). DOI:10.1007/s00520-014-2432-8 · 2.36 Impact Factor
  • H. Murata · T. Hattori · H. Maeda · S. Takashiba · M. Takigawa · J. Kido · T. Nagata ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and objective: Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. Material and methods: To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Results: Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. Conclusion: We identified TDP-43 as one of the novel TNF-α factors and found that it bound to the LPS-responsive element in the TNF-α promoter to increase TNF-α expression.
    Journal of Periodontal Research 09/2014; 50(4). DOI:10.1111/jre.12227 · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of “chronic inflammation”. Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.
    Odontology 08/2014; 103(3). DOI:10.1007/s10266-014-0172-3 · 1.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20μM and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2-signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p <0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.
    Bioorganic & Medicinal Chemistry 08/2014; 22(19). DOI:10.1016/j.bmc.2014.07.047 · 2.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been suggested that vitamin C deficiency/scurvy is associated with gingival inflammatory changes; however, the disorder is very infrequently encountered in the modern era. Here, we report a case of extensive gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection.
    08/2014; 2(6). DOI:10.1002/ccr3.114
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Key Clinical Message We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease.
    08/2014; 2(6). DOI:10.1002/ccr3.112
  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently reported frequent detection of antibiotic-resistant bacteria on the oral mucosa during the period of hematopoietic cell transplantation (HCT) and suggested an association between oral mucositis and antibiotic-resistant bacterial infection. Methicillin-resistant Staphylococcus spp. were frequently detected, and the oral cavity may be a reservoir of the gene mediating methicillin resistance, mecA. Here, we examined the frequency of mecA carriers in patients undergoing HCT. Fifty-nine patients (male (M) = 37, female (F) = 22, 47.3 ± 11.0 years) receiving HCT were enrolled in this study. Buccal swab samples were obtained four times from day -7 to day +20 (once/week), and mecA was detected by PCR. Fifty-two subjects without systemic disease, who completed dental treatment, especially periodontal treatment (M = 21, F = 31, 55.4 ± 14.2 years), were also enrolled as controls and checked for mecA on the oral mucosa. Seventy-six percent (45/59) of the HCT patients carried mecA at least once in the study period (days -7 to +20), while no control subjects had mecA. The frequency of mecA carriers was 19.2 % from days -7 to -1, while it was significantly increased on days +7 to +13 and +14 to +20, with frequencies of 60.9 and 63.2 %, respectively (P < 0.01, ANOVA). mecA was detected in oral mucosa of patients undergoing HCT. The high detection frequency of staphylococci resistant to penicillin and beta-lactams in our recent report was supported.
    Supportive Care in Cancer 02/2014; 22(6). DOI:10.1007/s00520-014-2151-1 · 2.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This case report describes the 26-year course of periodontal treatment for a woman suffering from generalized aggressive periodontitis since age 24, from the bacteriological, immunological, and clinical points of view. During this course, the patient experienced changes in her life stages such as marriage, moving, childbirths and childcare. Given the potential impact of lifestyle changes on the disease status, an attempt was made to detect the changes of the disease condition before clinical symptoms appeared by monitoring the fluctuations of serum IgG antibody titers against periodontopathic bacteria during the active phase of therapy to the phase of supportive periodontal therapy (SPT). We have discussed the pathological changes influenced by the events in each life stage and the consultations provided to support the patient during the phase of SPT. Based on our observations, we propose a method for long-term care of patients with aggressive periodontitis that begins in the late teens/early twenties. This proposal focuses on the control of oral infection based on the serum IgG antibody titers as an indicator of the disease activity caused by the chronic bacterial infection. Nihon Shishubyo Gakkai Kaishi (J Jpn Soc Periodontol) 56(2):217-226, 2014.
    Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) 01/2014; 56(2):217-226. DOI:10.2329/perio.56.217
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is necessary to suppress disease activity under strict infection control in the treatment of patients suffering from aggressive periodontitis, since they are at a high risk of developing periodontal infection. In particular, longitudinal infection control is important to apply orthodontic therapy to patients with pathologic tooth migration and tooth crowding. Nevertheless, no consensus exists on any clinical index for the initiation of orthodontic therapy in patients suffering from aggressive periodontitis. Here, we report a case of comprehensive periodontal therapy in a 22-year-old woman suffering from generalized aggressive periodontitis caused by Agregatibacter actinomycetemcomitans (Aa). We performed not only clinical examinations, but also measurement of the serum IgG antibody titers to periodontal bacteria and bacterial DNA testing by quantitative real-time polymerase chain reaction for immunological and bacteriological assessment of the periodontal infection and disease activity. In the re-evaluation of the effects of periodontal surgery, the bacterial DNA test showed no detection of Aa and also the IgG titer against Aa had decreased to the healthy control level. Thus, we were confident that our comprehensive periodontal therapy had resulted in significant reduction of the disease activity,and subsequently undertook orthodontic therapy. In the present case, we conclude that bacterial DNA testing and measurement of the serum IgG titers against Aa could provide certain evidence for determination of the initiation of orthodontic therapy in patients with generalized aggressive periodontitis. Nihon Shishubyo Gakkai Kaishi (J Jpn Soc Periodontol) 55(4):340-348, 2013.
    Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) 01/2014; 55(4):340-348. DOI:10.2329/perio.55.340
  • [Show abstract] [Hide abstract]
    ABSTRACT: Eosinophil cationic protein (ECP) was reported previously to be involved in allergic inflammation with cytotoxic activity. On the other hand, recent studies showed that ECP did not induce cell death but inhibited the growth of cancer-derived cells. Our previous study indicated that human ECP enhanced differentiation of rat neonatal cardiomyocytes and stress fiber formation in Balb/c 3T3 mouse fibroblasts, while the effects of human ECP on human fibroblasts are unknown. The present study was performed to determine the effects of human ECP on cytokine expression in human fibroblasts by protein array. The effects of recombinant human ECP (rhECP) on normal human dermal fibroblasts (NHDF) were examined by assaying cell growth. Furthermore, cytokine expression of NHDF stimulated by ECP, which could influence cell growth, was evaluated by protein array. ECP was not cytotoxic but enhanced the growth of NHDF. The peak rhECP concentration that enhanced the cell counts by 1.56-fold was 100 ng/mL, which was significantly different from cultures without ECP stimulation (ANOVA/ Scheffe's test, P < 0.05). Array analyses indicated that ciliary neurotrophic factor (CNTF), neutrophil-activating peptide (NAP)-2, and neurotrophin (NT)-3 were significantly upregulated in NHDF stimulated with 100 ng/mL ECP compared to those without stimulation. ECP is not cytotoxic but enhances the growth of NHDF. CNTF, NAP-2, and NT-3 were suggested to be involved in enhancing the growth of NHDF. These findings will contribute to determination of the role of ECP in allergic inflammation.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2013; 31(4):271-6. DOI:10.12932/AP0287.31.4.2013 · 0.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Porphyromonas gingivalis is a major etiological agent of periodontal diseases and the outer membrane vesicles (OMVs) contain virulence factors such as LPS and gingipains. In this study, we investigated the potential role of the OMVs in host immune response and tissue destruction during P. gingivalis infection. Firstly, we found that sera from periodontitis patients had significantly stronger reactivity against an OMV-producing wild type strain than the isogenic OMV-depleted strain. OMVs were found to be highly antigenic, as absorption of patient sera with OMVs greatly reduced reactivity with whole cells of P. gingivalis. LC-MS/MS analysis of OMVs revealed multiple forms of gingipains and several gingipain-related proteins. Western blots of OMVs using patient sera revealed a conserved immunoreactive antigen profile resembling the profile of OMV antigens that were recognized by gingipain antiserum, suggesting a potential role of OMV-associated gingipains in triggering antibody-mediated immune responses to P. gingivalis infection. When OMVs were added to a monolayer of an oral squamous epithelial cell line, OMVs caused cell detachment, which was inhibited by preincubating OMVs with anti-gingipain antiserum. These data suggest that gingipain-laden OMVs may contribute to tissue destruction in periodontal diseases by serving as a vehicle for the antigens and active proteases.
    Microbes and Infection 10/2013; 16(1). DOI:10.1016/j.micinf.2013.10.005 · 2.86 Impact Factor
  • M Shimoe · T Yamamoto · N Shiomi · K Tomikawa · S Hongo · K Yamashiro · T Yamaguchi · H Maeda · S Takashiba ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and objective: Spatiotemporal inhibition of apical migration and proliferation of gingival epithelium are significant factors involved in periodontal regeneration. Transforming growth factor β (TGF-β) is important in multiple aspects of wound healing, and Smad2, a downstream transcription factor of TGF-β, has an inhibitory effect on re-epithelialization during gingival wound healing. Therefore, we investigated the effects on migration and proliferation status, and intra/extracellular signaling regulated by Smad2 overexpression in gingival epithelial cells. Material and methods: Gingival epithelial cells were isolated from the palatal gingival tissue of transgenic mice overexpressing Smad2 driven by the Keratin14 promoter. Smad2 expression was identified by western blotting and immunofluorescence analysis. Scratch assay and 5-bromo-2'-deoxyuridine staining were performed to assess cell migration and proliferation. To inactivate TGF-β type I receptor, the cultures were supplemented with SB431542. Secreted TGF-β was quantified by ELISA. Smad2 target gene expression was examined by real-time RT-PCR and in vivo immunofluorescence analysis of gingival junctional epithelium. Results: Smad2-overexpressing cells were confirmed to have significant phosphorylated Smad2 in the nucleus. Scratch assay and 5-bromo-2'-deoxyuridine staining indicated that Smad2-overexpressing cells showed no significant differences in migration, but had reduced proliferation rates compared to wild-type controls. SB431542 significantly inhibited Smad2 phosphorylation, which coincided with restoration of the proliferation rate in Smad2-overexpressing cells. ELISA of TGF-β release did not show any differences between genotypes. The cell cycle inhibitors, p15 and p21, showed significant upregulation in Smad2-overexpressing cells compared to wild-type controls. Moreover, junctional epithelium of the transgenic mice showed increased expression of P-Smad2, p15 and p21. Conclusion: The signaling activation triggered by overexpression of Smad2 was dependent on TGF-β type I receptor, and the activated Smad2 increased p15 and p21 expression, responsible for inhibiting cell cycle entry, resulting in antiproliferative effects on gingival epithelial cells. Understanding of Smad2-induced signaling would be useful for possible clinical application to regulate gingival epithelial downgrowth.
    Journal of Periodontal Research 06/2013; 49(3). DOI:10.1111/jre.12106 · 2.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in molecular biological techniques have yielded large amounts of information regarding the oral microflora. The microbiological communities were shown to be more diverse than previously thought and to include a number of previously uncharacterized microorganisms. The range of research targets of microorganisms associated with oral diseases has been expanded to include these unknown or uncharacterized organisms. These organisms include the Archaea. A series of recent reports suggested these microorganisms to be potential pathogens involved in periodontitis and apical periodontitis mainly based on the detection frequency or their increased numbers in diseased sites in association with the severity or symptoms of disease. However, it cannot be concluded that Archaea are oral pathogens based on such circumstantial evidence. Further studies are required to investigate the potential pathogenic mechanisms of action of these organisms. This will require investigation of the antigenic properties of the Archaea and synergism with other established oral pathogens. Especially, studies of the host immune response will provide insight into the medical impact of Archaea as suspected pathogens.
    Japanese Dental Science Review 05/2013; 49(2):72–78. DOI:10.1016/j.jdsr.2013.01.002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Both group I (HSP60) and group II (CCT) chaperonins are targets of autoantibodies. Autoimmune reactions to HSP60 have been well characterized, while immune reactions to group II chaperonin have not been clarified. Methanobrevibacter oralis is a suspected periodontal pathogen with group II chaperonin. In this study, serum responses to M. oralis chaperonin, human HSP60, and CCT subunits were examined using sera from patients with periodontitis and autoimmune diseases. In comparison to healthy controls, periodontitis patients showed significantly higher responses to CCT4 and CCT8 on dot blot analysis. Signals for CCT3 and CCT8 in autoimmune disease patients were significantly higher than in controls. Significant differences were also demonstrated by Western blotting in anti-CCT4 response in both patient groups. All subjects showed strong reactivity to M. oralis chaperonin and faint signals to human HSP60. Autoantibodies were raised against CCT rather than HSP60, and CCT3, CCT4, and CCT8 were shown to be the main targets. Host immune systems may be frequently exposed to chaperonins of Archaea in various habitats. Although further studies of the cross-reactivity between M. oralis chaperonin and human CCT are required, anti-CCT autoantibodies may be involved in the pathogenesis of periodontitis and autoimmune diseases. This article is protected by copyright. All rights reserved.
    Pathogens and Disease 04/2013; 68(1). DOI:10.1111/2049-632X.12041 · 2.40 Impact Factor

Publication Stats

3k Citations
376.24 Total Impact Points


  • 1993-2015
    • Okayama University
      • • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      • • Division of Biological Science
      • • Medical School
      • • Department of Periodontal Science (Periodontology and Endodontology)
      Okayama, Okayama, Japan
  • 2010
    • Kobe Tokiwa University
      Kōbe, Hyōgo, Japan
  • 2001-2005
    • The University of Tokushima
      • • Institute for Genome Research
      • • Department of Periodontology and Endodontology
      Tokusima, Tokushima, Japan
  • 1999
    • Boston University
      • Department of Periodontology and Oral Biology
      Boston, MA, United States