S Takashiba

Okayama University, Okayama, Okayama, Japan

Are you S Takashiba?

Claim your profile

Publications (161)337.09 Total impact

  • [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; · 2.86 Impact Factor
  • Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 09/2014;
  • [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; · 1.58 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;
  • 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.
    Clinical Case Reports. 08/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Key Clinical MessageWe 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.
    Clinical Case Reports. 08/2014;
  • [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; · 2.09 Impact Factor
  • [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. · 0.79 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; · 2.92 Impact Factor
  • [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; · 1.99 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.
  • [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;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Dento-gingival junction is one of the crucial physical barriers against periodontal infection. Junctional epithelial adhesion is significantly important not only in prevention of periodontitis but also in regeneration of periodontal tissue. Transforming growth factor-β (TGF-β) controls numerous functions of epithelial cells by regulation of cell adhesion molecules such as integrins and extracellular matrix (ECM). Therefore, we examined the effect of TGF-β signaling on adhesion in gingival epithelial cells. Methods: Gingival epithelial cells were isolated from healthy human gingiva. An immortalized human gingival epithelial cell line (IHGE cells) was established by infection with a lentivirus vector containing simian virus 40. Cell adhesion assay was performed using TGF-β1-stimulated IHGE cells with or without an inhibitor of TGF-β type I receptor (TβRI) (SB431542) or mitogen-activated protein kinases (MAPK) (SB203580, PD98059, SP600125) respectively. After 24 h of culture, the IHGE cells were trypsinized, seeded in 96-well plates at 1×104 cells per well, and incubated for 1 h. Non-adherent cells were washed away with PBS, and the numbers of adherent cells were counted using Cellomics ArrayScan VTI. Moreover, mRNA accumulation of ECM and integrins were quantified by real-time RT-PCR. Results: The number of adherent cells was increased by TGF-β1 but there was no significant change by either MAPK inhibitors. In contrast, the numbers of adherent cells were significantly decreased by TβRI inihibitor. Accumulation of mRNA of integrins (α2, α5, β4, β6), tenascin-C, fibronectin-1 and versican were increased by TGF-β1, while decreased by TβRI inhibitor. Conclusion: This study indicated that TGF-β1 promoted gene expression of integrins and ECM, and cell adhesion ability in a TβRI-dependent manner in IHGE cells. Since TβRI activates Smad2/3, we conclude that TGF-β-Smad2/3 signaling is crucial for regulation of cell adhesion in gingival epithelial cells.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Increased expression of interleukin-6 (IL-6) is associated with a variety of diseases, including periodontitis. Caveolin-1 (Cav-1) is a scaffolding/regulatory membrane protein that interacts with signaling molecules in endothelial cells, fibroblasts, etc. Cathepsins are widely expressed as cysteine proteases involved in intracellular proteolysis. We have reported previously that the role of Cav-1 on cathepsin-B and -L production, and also on enzymatic activity of cathepsin-B and -L in human gingival fibroblasts (HGFs) stimulated by IL-6 in the present of soluble form of IL-6 receptor (sIL-6R) (J Cell Physiol, 2008). Enzymes secreted by cells are involved in remodeling of extracellular matrix, and may cause gingival tissue destruction in periodontitis. In this study, we investigated the role of Cav-1 on cathepsin-B and -L secretion by HGFs stimulated by IL-6/sIL-6R. Method: The siRNA-mediated Cav-1 down-regulating system was established by transient transfection of Cav-1 siRNA (100 nM) to HGFs. Using this system, the Cav-1 down-regulated cells were pretreated with p44/42 MAPK inhibitor PD98059 and JNK inhibitor SP600125 (50 µM each), and treated with IL-6/sIL-6R (50 ng/ml each) for 48 h. Culture supernatants were collected for immunoblotting analysis to examine cathepsin-B and -L secretion. Result: IL-6/sIL-6R increased cathepsin-B and -L secretion from HGFs. As compared with these results using control siRNA-transfected HGFs, cathepsin-B and -L secretion were also significantly suppressed in Cav-1 down-regulated HGFs. Inhibition of JNK significantly diminished the secretion of both cathepsin B and L induced by IL-6/sIL-6R. On the other hand, P44/42 MAPK inhibition diminished only cathepsin B secretion (ANOVA/Sheffe’s test, p<0.05). Conclusion: Cav-1 is required for the secretion of cathepsin-B and -L in HGFs stimulated with IL-6/sIL-6R. Our findings indicate that Cav-1 would be a therapeutic target for IL-6-induced tissue destruction in periodontitis.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Periodontal ligament fibroblastic cells (PDL cells) contain progenitors inducing periodontal regeneration. It is crucial to exert spatiotemporally fine-tuned control of switching from growth to differentiation in PDL cells. Transforming growth factor β (TGF-β) controls pleiotropic cellular functions in a tissue-specific manner; cell proliferation in mesenchyme is mostly induced. We previously reported that Smad2, a downstream signaling of TGF-β, has inhibitory effects on gingival epithelial proliferation. We aimed to examine the effect of Smad2 on proliferation and differentiation of PDL cells. Methods: PDL cells were obtained from human extracted teeth. smad2-overexpressing PDL cells (smad2-PDL cells) were established by gene transfection using lipofection. After 24 h, the expression of smad2, smad3, and proliferating cell nuclear antigen (pcna) was monitored by real-time PCR. Moreover, comprehensive analysis of gene expression was performed using a PCR array for osteogenesis-related genes. The culture supernatant was analyzed for the products of these genes by enzyme-linked immunosorbent assay. Results: smad2-PDL cells were confirmed to increase smad2 mRNA accumulation, which coincided with increased pcna mRNA while smad3 mRNA remained unchanged. Array analysis indicated that 12 genes were up-regulated more than 2-fold in smad2-PDL cells while 9 genes were down-regulated. Importantly, fibroblast growth factor 2 (fgf2) was up-regulated 6.4-fold while osteogenesis-related genes such as bone morphogenetic protein 2 and alkaline phosphatase remained baseline levels. Moreover, secreted FGF2 was significantly increased in smad2-PDL cells. Conclusion: It is critical to understand signaling mechanisms that not only induce proliferation of PDL cells but also simultaneously inhibit proliferation of gingival epithelial cells, for periodontal regeneration. Our study demonstrated that FGF2 secretion was increased in smad2-PDL cells. Since Smad2 has inhibitory effects on epithelial proliferation, we conclude that Smad2 could contribute periodontal regeneration by enhancement of FGF2 signaling.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • A. IKEDA, J. MINESHIBA, H. MAEDA, S. TAKASHIBA
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Saliva prevents oral infections, and acts important roles to maintain intraoral environment. Salivary gland lacks regenerative capacity, thus it is hard to recover its functions after any kinds of damage. Recently, it is reported that CD49f-positive epithelial cells of salivary glands have the differentiation potency for endodermal cells such as liver and pancreas(Okumura et al., Hepatology,2003). Thus, we hypothesized that the extracellular humoral factors secreted by CD49f-positive cells would be potential progenitor cells related to regeneration of salivary glands. Method: CD49f-positive cells derived from submandibular glands of five-week-old male C57BL/6 mice were fractionated by magnetic cell sorting. The expression of CD49f and the intracellular synthesis of laminin were confirmed by immunofluorescence cytochemistry. Profiles of the RNA expression in the cells were analyzed using Mouse Growth Factors RT² Profiler™ PCR Array. Based on these results we examined the differences of expression of inhibin βB, inhibin βA, inhibin α, and follistatinby real-time RT-PCR analyses, and also examined the protein expression of them between CD49f-positive and CD49f-negative epithelial cells of salivary glands by Western blot analyses. Result: CD49f-positive cells accounted for approximately 10 % of the cells isolated from submandibular glands. These cells also expressed intracellular laminin. PCR Array allowed us to pick up 12 factors. Gene expression of inhibin βA, inhibin βB, and follistatin of CD49f-positive cells was significantly higher than those of CD49f-negative cells. However, protein expression of Inhibin βA, and Inhibin βB in CD49f-positive cells was significantly higher than CD49f-negative cells, but Follistatin was not. Conclusion: These data suggest that Inhibin βA, Inhibin βB, and Follistatin may relate to the proliferation of CD49f-positive cells, and that CD49f-positive cells could be progenitor cells in salivary glands.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Gingival epithelium attaches to the tooth by hemidesmosomes using integirn and extracellular matrix (ECM), and it is a physical barrier against bacterial invasion. Once the attachment is destroyed by bacterial infection, inflammation spreads deeply into periodontal tissue. We already reported that Aggregatibacter actinomycetemcomitans Y4 (Aa) decreased cell adhesion and expression level of many integrins in gingival epithelial cells. Interestingly, Integrin α5 increased in this condition. We hypothesized that Integrin α5 may play a crucial role against infection by altering cell adhesion among gingival epithelial cells during Aa infection. Method: Gingival epithelial cells were isolated from human periodontal tissue and immortalized by transfection of Simian virus 40 using a lentivirus vector. Cells infected with Aa were cultured with or without neutralizing antibody against Integrin α5 for 24 hours. Subconfluent cells were trypsinized, and then seeded in 96-well plates of 1×104 cells per well. After 1-hour incubation, non-adherent cells were washed away with PBS. The cells were stained and counted using Cellomics ArrayScan VTI. We also examined gene expression level of integrins and ECM by quantitative RT-PCR. Result: The number of adherent cells were significantly decreased by Aa infection but not decreased with the antibody neutralizing Intergrin α5. The expression level of integrin α2, α3, β6 and fibrinectin-1 were decreased by Aa infection but not decreased with the antibody. Conclusion: It is considered that integrins play an important role not only for cell adhesion by physiologically binding to ECM but also as receptors associated with signal transduction. Thus, our results suggest that Integrin α5 would act as a receptor for the signals transduced intracellularly to regulate other integrins and ECM expression during Aa infection.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases. Therefore, efficient screening of patients is essential for general health. This study was performed to evaluate prospectively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens. Oral examination was performed, and IgG titers against periodontal pathogens were measured by ELISA in 1,387 individuals. The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis, and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated. The relationships between IgG titers and severity of periodontitis were analyzed. The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682. Both clinical parameters and IgG titers decreased significantly under periodontal treatment. IgG titers of periodontitis patients were significantly higher than those of healthy controls, especially in those with sites of probing pocket depth over 4 mm. Multiplied cut-off values were useful to select patients with severe periodontitis. A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients (ClinicalTrials.gov number NCT01658475).
    Journal of dental research 09/2012; · 3.46 Impact Factor
  • Supportive Care in Cancer 09/2012; · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Osteoblasts play a central role in bone formation during healing phase of periapical periodontitis. Adhesion of osteoblasts to extracellular matrix (ECM) initiates osteogenesis at periapical lesion. Integrins compose a superfamily of cell surface receptors involved in cell-cell and cell-matrix adhesion. We have reported previously that interleukin (IL)-1α increased during healing phase in a rat experimental root canal treatment model (Martinez et al, 2007). However, biological roles of IL-1α on periapical healing are still unknown. In this study, we investigated IL-1α-induced integrin expression, adherence and osteogenesis in osteoblasts to clarify possible mechanisms of periapical healing. Methods : ECM genes expression pattern during healing phase in rat experimental periapical lesion were analyzed by DNA microarray. Mouse osteoblastic cells, MC3T3-E1, were treated with IL-1α (0-10 ng/ml) for 48 h, and cells were seeded in ECM (laminin or fibronectin)-coated culture plates. After 1 h incubation, non-adherentcells were removed and adherent cells were stained with crystal violet. Also, cells were treated with IL-1α for 48 h, and total cell lysates were collected to monitor integrin subunits expression by Western blotting. In addition, to investigate the effects of IL-1α for osteogenesis, cells were pre-treated with IL-1α (0.1 ng/ml), seeded in ECM-coated plates, and cultured for 5 weeks. Calcium productivity was monitored by von Kossa staining. Results : During periapical healing phase, laminin γ2 gene expression was up-regulated dramatically compared to inflammation phase. IL-1α enhanced MC3T3-E1 attachment to a laminin-coated plate significantly compared to that of fibronectin or poly-D-lysine-coated plates (p<0.05). Also, IL-1α enhanced integrin α3 protein expression, but not α6, β1, β4 (p<0.05). Furthermore, IL-1α enhanced calcium production in laminin-coated plates compared to that of other coated plates. Conclusion: Our findings suggest that IL-1α may enhance integrin α3 expression and attachment to laminin for inducing osteogenesis in osteolbasts during periapical healing.
    IADR General Session 2012; 06/2012

Publication Stats

2k Citations
337.09 Total Impact Points

Institutions

  • 1997–2013
    • Okayama University
      • • Department of Periodontal Science (Periodontology and Endodontology)
      • • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      Okayama, Okayama, Japan
  • 2011
    • Iwate Medical University
      Morioka, Iwate, Japan
  • 2010
    • Hyogo College of Medicine
      • Department of Surgical Pathology
      Nishinomiya, Hyogo-ken, Japan
  • 1999
    • Boston University
      • Department of Periodontology and Oral Biology
      Boston, MA, United States