Takashi Takata

Hiroshima University, Hirosima, Hiroshima, Japan

Are you Takashi Takata?

Claim your profile

Publications (232)565.75 Total impact

  • Hiroko Oka, Masae Kitagawa, Takashi Takata
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: F-spondin, known as a secreted neuronal glycoprotein, is highly expressed on the tooth root surface and we had reported F-spondin is one of the specific markers of cementoblasts in periodontal tissue. In chronic periodontitis, significant cemental resorption rarely occurs on the root side, although alveolar bone resorption by osteoclasts is one of the major pathologic changes. Thus, we hypothesized that secretory F-spondin from cementoblasts might be involved in differentiation of clastic cells on the root surface. We studied effects of secretory F-spondin from F-spondin expressed cells and its pathway on receptor activator of NF-κB ligand (RANKL)-mediated differentiation of clastic cells. Methods: We used osteoclast precursors in this study. With a chamber assay, we examined effects of secretory molecules from F-spondin expressed cells of transgenic mice on RANKL-induced clastic cells' differentiation. Results: Secretory molecules from F-spondin overexpressed cells significantly inhibited the RANKL-mediated tartrate-resistant acid phosphatase (TRAP) positive cells from primary progenitor cells with the camber system. F-spondin suppressed RANKL-mediated NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1), TRAP, Cathepsin K and DC-STAMP (dendritic cell-specific transmembrane protein) expressions on the cells. The suppressive effect of F-spondin on RANKL-induced differentiation of clastic cells was partially blocked by knockdown of low-density lipoprotein receptor-related protein 8 (LRP8). Conclusion: Our findings indicate that secretory factors from F-spondin expressed cells, including F-spondin, downregulates differentiation of clastic precursors. Moreover, F-spondin inhibits RANKL-mediated differentiation of clastic cells partially via LRP8. It is suggested that secretory F-spondin may act protectively from cemental resorption partially via LRP8 in periodontal tissue.
    Journal of periodontology. 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it. We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system. Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation. bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.
    Archives of oral biology 02/2014; 59(2):226-32. · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain-derived neurotrophic factor (BDNF) activates its receptor TrkB, and promotes neuronal survival, differentiation, and synaptic functions. Furthermore, we have revealed that BDNF can also regulate cementoblast differentiation and cellular survival via TrkB–ERK/Akt signaling cascade, which, in turn, results in the induction of periodontal tissue regeneration. Recently, using in silico screening with a BDNF loop-domain pharmacophore, a small molecule BDNF mimetic, called LM22A-4 that can facilitate TrkB signaling in hippocampal neurons to prevent cell death, was identified. Therefore, this study aimed to investigate the effect of LM22A-4 on cementoblast differentiation and its molecular mechanism. LM22A-4 and BDNF stimulation was found to enhance OPN, ALPase, and OC mRNA expression in immortalized human cementoblast-like (HCEM) cells, indicating cementoblast differentiation. In addition, similar to this result, both LM22A-4 and BDNF treatment facilitated TrkB phosphorylation and TrkB binding to adaptor proteins, such as Shc, GRB2, and SOS1, indicating TrkB activation. Importantly, the downstream target ERK and Akt was also phosphorylated by LM22A-4 and BDNF stimulation. Moreover, BDNF mimetic stimulation transactivated ERK from the cytoplasm into the nuclei in HCEM cells. It is noteworthy that a tyrosine kinase receptor inhibitor, K252a, an MEK–ERK inhibitor (U0126), and a PI3Kinase–Akt inhibitor (LY294002) remarkably attenuated TrkB, ERK, and Akt phosphorylation as well as increase of OPN mRNA expression in the HCEM cells, respectively. These findings suggest that the small molecule BDNF mimetic LM22A-4 regulates cementoblast differentiation via the TrkB–ERK/Akt signaling cascade. Therefore, this small compound may lead to the development of a novel therapeutic approach for periodontal tissue regeneration.
    International immunopharmacology 01/2014; · 2.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity.
    PLoS ONE 01/2014; 9(10):e110519. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression that provides cancer cells with the ability to escape from the primary focus, invade stromal tissues and migrate to distant regions. Cell lines that lack E-cadherin show increased tumorigenesis and metastasis, and the expression levels of E-cadherin and Snail correlate inversely with the prognosis of patients suffering from breast cancer or oral squamous cell carcinoma (OSCC). Moreover, recent studies have shown that most EMT cases are regulated by soluble growth factors or cytokines. Among these factors, fibroblast growth factors (FGFs) execute diverse functions by binding to and activating members of the FGF receptor (FGFR) family, including FGFR1-4. Fibroblast growth factor receptor 1 is an oncoprotein that is involved in tumorigenesis, and PD173074 is known to be a selective inhibitor of FGFR1. However, the roles of FGFR1 and FGFR1 inhibitors have not yet been examined in detail.Methods:Here, we investigated the expression of FGFR1 in head and neck squamous cell carcinoma (HNSCC) and the role of the FGFR1 inhibitor PD173074 in carcinogenesis and the EMT process.Results:Fibroblast growth factor receptor 1 was highly expressed in 54% of HNSCC cases and was significantly correlated with malignant behaviours. Nuclear FGFR1 expression was also observed and correlated well with histological differentiation, the pattern of invasion and abundant nuclear polymorphism. Fibroblast growth factor receptor 1 was also overexpressed in EMT cell lines compared with non-EMT cell lines. Furthermore, treatment of HOC313 cells with PD173074 suppressed cellular proliferation and invasion and reduced ERK1/2 and p38 activation. These cells also demonstrated morphological changes, transforming from spindle- to cobble stone-like in shape. In addition, the expression levels of certain matrix metalloproteinases (MMPs), whose genes contain activator protein-1 (AP-1) promoter sites, as well as Snail1 and Snail2 were reduced following PD173074 treatment.Conclusion:Taken together, these data suggest that PD173074 inhibits the MAPK pathway, which regulates the activity of AP-1 and induces MET. Furthermore, this induction of MET likely suppresses cancer cell growth and invasion.British Journal of Cancer advance online publication, 17 September 2013; doi:10.1038/bjc.2013.550 www.bjcancer.com.
    British Journal of Cancer 09/2013; · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Tooth loss is a critical risk factor for oral hypofunction. The prevalence of chronic periodontitis is still high and is the most causative factor of tooth loss leading indigestion. Therefor inhibiting tooth loss is inevitable for better quality of life. To explore new candidate molecules evaluating periodontal disease activity for early treatment intervention, proteomic analysis was applied to the pocket exudate (PE) of periodontal patient. Method: The proteomic analysis of PEs of 2 patients with severe periodontitis was performed in comparison with gingival crevicular fluid of a healthy volunteer. The mRNA levels of some proteins specifically expressed in PE were examined in resected gingival tissues obtained from 7 periodontitis, 2 gingivitis patients and 2 healthy volunteers and were compared with those of proinflammatory cytokines like TNF-α, IL-1β and IL-8. Result: Fifteen proteins including heat shock 70kDa protein 2 (Hspa2), heat shock 70kDa protein 5 (Hspa5), Snif2-related CREBBP activator protein (SRCAP), myeloid cell nuclear differentiation antigen (MNDA), Down syndrome cell adhesion molecule like 1 (Dscaml1), fibroblast activation protein-alpha (FAPα) were specifically detected in PE. Among these candidate molecules for periodontal disease activity Hspa2, Hspa5, SRCAP and MNDA were upregulated in 4 periodontitis and 2 gingivitis specimens, in which TNF-α, IL-1β and IL-8 were upregulated. FAPα was expressed only in periodontitis with proinflammatory cytokine-expression. In 2 healthy gingival tissues and 3 periodontitis specimens without the cytokine-expression, the levels of candidate molecules were very low. All tissue specimens examined showed no mRNA expression of Dscaml1. MNDA-immunolocalization was seen in periodontitis specimens with severe neutrophil infiltration. Conclusion: The candidate molecules, Hspa2, Hspa5, FAPα, SRCAP and MADA, showed the positive correlation with proinflammatory cytokines-expression, which are known as indicators of periodontal disease activity. Moreover, MNDA-upregulation in PE may be related to acute exacerbation of periodontitis. These molecules may be useful makers for periodontal disease activity.
    IADR Asia/Pacific Region (APR) Regional Meeting and Co-Annual Scientific Meeting of IADR Divisions 2013; 08/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine anti-inflammatory roles of F-spondin (SPON1), that we first determined to be expressed in cementoblasts, in periodontitis, we examined effects of SPON1 on expression of inflammatory cytokines and the destruction of periodontal tissues induced by lipopolysaccharide (LPS). Method: We used immortalized human cementoblast-like cell lines (HCEM), human periodontal ligament cell lines (HPL) and HPL-F-spondin cells transfected with a retroviral plasmid encoding rat SPON1 cDNA into HPL (HPL-SPON1). SPON1 expression of HCEM was knock-downed by siSPON1. To investigate the effect of SPON1 on inflammation induced by LPS in these cells, we examined expression of inflammatory cytokines mRNAs by RT-PCR and phosphorylation of Erk expression by western blot. We furthermore compared inflammatory reactions of periodontal tissues induced by LPS in SPON1 transgenic mice (SPON1-TG) with those in wild type mice (WT). Result: LPS treatment up-regulated SPON1 expression and down-regulated IL-6 expression in HCEM. Expression of TNF-α, IL-1ß and IL-8 didn’t show remarkable change with or without LPS treatment. Transfection of siSPON1 recovered down-regulation of IL-6 induced by LPS in HCEM. Furthermore, IL-6 expression was significantly decreased in HPL-SPON1. Phosphorylation of Erk induced by LPS was detected in HPL, but not in HPL with SPON1 transfection. SPON1 may down-regulate IL-6 expression through inhibiting activation of Erk pathway. In vivo, the number of mature osteoclasts and neutrophils induced by LPS in the periodontal tissue were fewer in SPON1-TG than in WT. SPON1-TG showed less bone destruction than WT. Conclusion: We conclude that SPON1 may play anti-inflammatory action in periodontitis by down-regulation of IL-6 expression. SPON1 in the cementoblasts may protect cementum from pathologic resorption. This may explain the reason why cementum is not so common a feature of periodontitis-involved teeth comparing to bone resorption. SPON1 may be a novel molecule applicable for prevention and treatment of periodontal inflammation and destruction.
    IADR Asia/Pacific Region (APR) Regional Meeting and Co-Annual Scientific Meeting of IADR Divisions 2013; 08/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The pleiotropic functions of bovine lactoferrin (bLF) are known but poorly understood. bLF has been reported to stimulate osteoblast proliferation, enhance thymidine incorporation into osteocytes, and reduce apoptosis of osteoblasts. However, the essential effects of bLF on bone cell anabolism and related mechanism are not well demonstrated. Method: C3H10T1/2, a mouse mesenchymal cell line, and primary osteoblasts were cultured in a-MEM. In vitro study, alkaline phosphatase (ALP) activity, mineralized nodule formation as well as the expression of osteoblast differentiation markers were examined. Western blotting analysis, immunoprecipitation and binding assay were performed to clarify the bLF-induced signal transduction mechanisms. In ex vivo organ cultures of mouse calvariae were also performed. Result: bLF enhanced ALP activity and the expression of early osteoblastic differentiation markers, Runx2, ALP and Osterix, in C3H10T1/2. bLF also up-regulated ALP activity, mineralized nodule formation and the expression of late osteoblastic differentiation markers, BSP and OCN, in primary osteoblasts. Furthermore, bLF induced Smad-dependent and Smad-independent MAPK activation. Both ALP activity and mineralized nodule formation induced by bLF treatment were eliminated in TGF-b receptor (TbR)-Ⅰ and p38 kinase inhibitor treated cells. The direct binding of bLF to TbRⅡ was also observed. In ex vivo experiments, it was revealed that bLF promoted new bone formation and regenerating of bone defects. Conclusion: Our data suggest that bLF is a potent osteogenic factor, which exerts its actions by activating the TGF-b signaling pathway. Our data indicate that bLF has distinct anabolic effects on the development and growth of osseous tissue in mammals. We anticipate that bLF will be a valuable agent for bone regeneration.
    IADR Asia/Pacific Region (APR) Regional Meeting and Co-Annual Scientific Meeting of IADR Divisions 2013; 08/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm that arises in subcutaneous tissue, with that in the oral cavity extremely rare. We present a case of malignant OFMT in the tongue. A 26-year-old male noticed a painless mass in the tongue, which was extracted at a general hospital. Four years later, the tumor recurred and was resected at our department. Histologically, the recurrent tumor was composed of the closely packed cells positive for vimentin and S-100 proliferating in a nodular fashion. It showed high cellularity and mitotic activity. In the primary tumor, some tumor cells were arranged in a diffuse or cord-like manner within an abundant fibromyxoid matrix, along with a small amount of metaplastic ossification, corresponding with the histopathological characteristic of OFMT. Accordingly, a diagnosis of malignant OFMT arising in typical OFMT was established. This is the first reported case of malignant OFMT in the tongue. Long-term follow-up is needed for confirmation of prognosis and biological behavior.
    Head & Face Medicine 06/2013; 9(1):16. · 0.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side-effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which ubiquitylates the cell cycle related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by downregulating geminin via APC/C activation. At present anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of X-rays irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation.
    Journal of Biological Chemistry 05/2013; · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Steatosis is a common liver expression of metabolic syndrome. 15`20% of patients progress to non-alcoholic steatohepatitis (NASH). In addition, NASH is associated with cirrhosis and hepatic carcinoma. Recently, it is accepted that gut-derived bacterial products play a role in NASH progression. However the relationship between periodontal pathogen and NASH is unknown. We investigated the effect of Porphyromonas gingivalis (P.g.) on progression of NASH in vivo and in vitro study. Method: In vivo experiments, C57BL/6J mice were fed either chow-diet (CD) or high-fat diet (HFD) for 12 weeks and then half of the mice in each group were infected with P.g. from the dental pulp (HFD-P.g.(-), HFD-P.g.(+), CD-P.g.(-) and CD-P.g.(+)). Histological findings and cytokine profile in liver were analysed. In vitro experiments, human hepatocytes (HC), myofibroblasts (MF) and macrophages, which are liver constitutive cells, were used. We examined the effects of P.g. -LPS on these cells with and without free fatty acid (FFA)-pretreatment in comparison with those caused by E. coli-LPS (E.c.-LPS). Result: After 6 weeks of infection, serum levels of LPS increased in P.g.(+)-groups. Steatosis developed in HFD groups and the foci of Mac2(+) macrophages were prominent in HFD-P.g.(+). P.g. was localized in Kupffer cells and hepatocytes and interestingly, areas of fibrosis only existed in HFD-P.g.(+). FFA-pretreatment upregulated TLR2 (P.g.-LPS receptor) expression in HC, MF (markedly) and macrophage (slightly), whereas TLR4 expression in them didn’t change. E.c.-LPS prominently increased some cytokines expression level from FFA-treated them whereas FFA-pretreatment did not affect E.c.-LPS induced cytokine production levels by them. Conclusion: In steatotic liver, dental infection of P.g. exacerbates the pathological progression of NASH through enhancement of sensitivity to P.g.-LPS by increasing TLR2. Our findings suggest that periodontal therapy may be beneficial impact on NASH.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Porphyromonas gingivalis (Pg), which is the main periodontal pathogen, is detected not only in periodontal plaque but also in infected pulp chamber. Recently, epidemiological studies revealed a link between periodontal disease and preterm delivery of low birth weight (PTLBW), however, the mechanism between Pg and PTLBW remain unclear. The present study was aimed to estimate the influence of Pg on PTLBW using Pg dental infection mouse model and further investigate the detailed mechanism by in vitrostudy. Method: In vivo experiment:8-wks-old♀C57Bl/6J mice were infected with Pg-w83-strain(108 CFU) from the pulp chamber (Pg+). Mating was started at 6wks post-infection when periapical granuloma was established. Gestational day (gd) and birth weight were examined and placental tissues were harvested from gd15 mice for immunohistochemical staining and PCR. Serum, placental tissue and amniotic fluid were collected for ELISA of cytokines. Uninfected mice were used as negative control (Pg-). In vitro experiment:HTR-8 (trophoblast), HuhT1 (endothelial cell) and THP1 (monocyte) cell lines were used to assess the effect of Pg /Pg-LPS. Result: Pg+ showed 2days of preterm birth (p<0.01) and low birth weight (p<0.01) compared with Pg-. The amnion-epithelium was damaged in Pg+ and trophoblasts and endothelium became degenerative. Moreover, galectin-3 (an immune regulator) suffused the whole placental tissue and dramatically increased in amniotic fluid (P<0.01). The weaker immuno-expression of CD-31 indicated endothelial damage and immuno-expression of COX-2 and TNF-a increased in placental tissue of Pg+. Pg was detected in placental tissue. It invaded into trophoblasts and endothelial cells and induced apoptosis of them in vitro experiment. Pg-LPS up-regulated the expressions of COX-2, TNF-a and galectin-3. Moreover, recombinant galectin-3 stimulation further increased expressions of them. Conclusion: In our mouse model, dentally applied Pg reaches placental tissue through blood circulation and induces PTLBW in which galectin-3 acts as an important immune regulator.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Ameloblastin (AMBN), the most abundant non-amelogenin enamel matrix protein, has a role in enamel matrix mineralization and ameloblast differentiation. Recently, it was reported that AMBN was expressed in bone tissue. We clarified that AMBN induced osteogenic differentiation through AMBN-CD63-Integrinβ1-Src axis by using osteosarcoma (OS) cell lines (Mol Cell Biol. 2011). During those experiments, we found that the AMBN-overexpressing OS cells showed suppression of proliferation and migration. Therefore, we have made a hypothesis that AMBN plays a tumor suppressive role in OS and performed following experiments to verify the hypothesis. Method: Tissue samples of 37 OS cases retrieved from Hiroshima University Hospital were used for correlating immunoexpression of AMBN and prognosis of patients. In vivo experiments, 143-B cells were injected into five-week-old male BALB/cAnNCrlCrlj mice, and tumor growth and metastasis were analyzed by bioluminescent imaging. In vitro experiments, western blot, wound healing assay and immunofluorescence were used for molecular analyses of AMBN bioactivities. Result: (1) In immunohistochemical analysis of 37 clinical OS cases, AMBN expression showed lower frequency of pulmonary metastasis (chi-square test, P<0.05) and better prognosis. (2) In vivo, AMBN significantly inhibited tumor growth and pulmonary metastasis of OS by using mouse xenograft model. 3) In vitro, AMBN induced cell cycle arrest in G1 phase and suppressed proliferation of OS cells through the reduction of c-myc expression triggered by Src inactivation. In addition, AMBN suppressed the migration activity with focal adhesion and stress fiber formation via RhoA activation induced by Src inactivation. (t-test, P<0.05). Conclusion: We demonstrate that AMBN has a new role as a tumor suppressor gene via Src inactivation in OS. Our findings indicate that AMBN has a potential to be used as a new prognostic marker and a therapeutic target of OS. (This study was supported by JSPS.)
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Brain-derived neurotrophic factor (BDNF) activates its receptor trkB, promoting neuronal survival, differentiation, and synaptic function. Moreover, we have revealed that BDNF can also regulate cementoblast differentiation via trkB-ERK signaling cascade, which, in turn, results in the induction of periodontal tissue regeneration. Otherwise, very recently, using in silico screening with a BDNF loop-domain pharmacophore, small molecule BDNF mimetic, LM22A-4, which can facilitate trkB signaling in hippocampal neurons to prevent cell death, was identified. Therefore, this study aimed to investigate the effect of BDNF mimetic small compound, LM22A-4 on cementoblasts differentiation and its molecular mechanism. Method: LM22A-4 was chemically synthesized. Immortalized human cmentoblast-like cells (HCEMs), established with transfection of hTERT gene were used in the following experiments. HCEMs were exposed to LM22A-4 in the presence or absence of K252a, which is a tyrosine kinase receptor specific inhibitor. The mRNA expressions of osteopontin (OPN), alkaline phosphatase (ALP) and osteocalcin (OC) were analyzed by real-time PCR. The phosphorylation of ERK was measured by Western blotting. Result: LM22A-4, as well as BDNF stimulation, enhanced the mRNA expression of OPN, ALP, and OC in HCEMs. In addition, similar to this result, both LM22A-4 and BDNF treatment elevated the phosphorylation of ERK. It is noteworthy that a tyrosine kinase receptor inhibitor, K252a remarkably abrogated the increase of the mRNA levels and ERK phosphorylation. Conclusion: These findings suggested that small molecule BDNF mimetic, LM22A-4, regulates cementoblast differentiation through trkB-ERK signaling pathway. Therefore, this small compound may lead to the development of therapeutic novel approach for the periodontal tissue regeneration.
    IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibro-osseous lesions of the jaw are poorly understood because of a significant overlap of clinical, radiological and histological features among the various types, though they present distinct patterns of disease progression. An ossifying fibroma is associated with significant cosmetic and functional disturbances, as it shows expansive proliferation. Thus, it is important to establish a specific marker, as well as clearly elucidate its etiology for diagnosis and proper treatment. We previously established immortalized cell lines from human ossifying fibromas of the jaw and found that they highly expressed the receptor for hyaluronan (HA)-mediated motility (RHAMM). In this study, we examined the expression of RHAMM mRNA in 65 fibro-osseous lesions, including ossifying fibroma, fibrous dysplasia and osseous dysplasia, as well as 5 normal jaws, using real-time RT-PCR and immunohistochemistry assays. RHAMM mRNA and protein expression were significantly elevated in the ossifying fibroma specimens. These results suggest that detection of upregulated RHAMM expression in an ossifying fibroma assists with differential diagnosis and has a key role in elucidation of its pathophysiology.
    Histology and histopathology 02/2013; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Root resorption is an adverse outcome of orthodontic tooth movement. However, there have been no available approaches for the protection and repair of root resorption. The aim of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on root resorption during experimental tooth movement and the effects of LIPUS in the RANKL/OPG mechanism in osteoblasts and cementoblasts in vitro. Twenty four Wistar strain male rats of 12-week-old were used in this study. The upper first molars were subjected to experimental movement in the mesial direction for 1-3 weeks. Through the experimental periods, the right upper first maxillary molar was exposed to LIPUS (LIPUS group) every day for 1, 2 or 3 weeks. The nature of root resorption was observed and then quantified by histomorphometric analysis. In the 2 weeks period, significantly greater amount of tooth movement was observed in the LIPUS group (P<0.05). In addition, LIPUS group showed less root resorption lacunae and lower number of odontoclasts. In the period of 3 weeks, LIPUS group presented significantly shorter length of root resorption lacunae and smaller amount of root resorption area (P<0.01). The number of odontoclasts and osteoclasts was also significantly lower in the LIPUS group (P<0.01 and P<0.05, respectively). However, no significant differences could be found regarding the amount of tooth movement. It is shown that LIPUS exposure significantly reduced the degree of root resorption during tooth movement without interrupting tooth movement. In vitro experiments showed that MC3T3-1 constitutively expressed higher levels of RANKL and RANTES mRNA comparing to OCCM-30. However, OPG mRNA expression was much higher in OCCM-30. LIPUS stimulation significantly increased the mRNA expression of RANKL in MC3T3-E1 at 4 (p<0.01) and 12 hours (p<0.05), although OPG mRNA expression was not affected by LIPUS. In contrast, the expression of RANKL and OPG mRNAs were both significantly increased by LIPUS in OCCM-30 at 12 hours (p<0.01). Moreover, LIPUS application suppressed the up-regulation of RANKL mRNA induced by compression force in OCCM-30, but no similar effect could be observed in MC3T3-E1. In conclusion, it is suggested that LIPUS exposure significantly reduces root resorption by the suppression of cementoclastogenesis by altering OPG/RANKL ratio during orthodontic tooth movement without interfering tooth movement. LIPUS may be an effective tool to prevent root resorption during tooth movement and is applicable to clinical use in near future.
    Bone 01/2013; · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: We investigated the effects of dental infection with Porphyromonas gingivalis (P.g.), an important periodontal pathogen, on NASH progression, by feeding mice a high fat diet (HFD)and examining P.g. infection in the liver of NASH patients. METHODS: C57BL/6J mice were fed either chow-diet (CD) or HFD for 12 weeks, and then half of the mice in each group were infected with P.g. from the pulp chamber (HFD-P.g.(-), HFD-P.g.(+), CD-P.g.(-) and CD-P.g.(+)). Histological and immunohistochemical examinations, measurement of serum lipopolysaccharide (LPS) levels and ELISA for cytokines in the liver were performed. We then studied the effects of LPS from P.g. (P.g.-LPS) on palmitate-induced steatotic hepatocytes in vitro, and performed immunohistochemical detection of P.g. in liver biopsy specimens of NASH patients. RESULTS: Serum levels of LPS are upregulated in P.g.(+) groups. Steatosis of the liver developed in HFD groups, and foci of Mac2-positive macrophages were prominent in HFD-P.g.(+). P.g. was detected in Kupffer cells and hepatocytes. Interestingly, areas of fibrosis with proliferation of hepatic stellate cells and collagen formation were only observed in HFD-P.g.(+). In steatotic hepatocytes, expression of TLR2, one of the P.g.-LPS receptors, was upregulated. P.g.-LPS further increased mRNA levels of palmitate-induced inflammasome and proinflammatory cytokines in steatotic hepatocytes. We demonstrated for the first time that P.g. existed in the liver of NASH patients with advanced fibrosis. CONCLUSIONS: Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g.-LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.
    Journal of Gastroenterology 01/2013; · 3.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which targets geminin for proteasomal degradation to allow pre-replicative complex formation. Conversely, from S to G2, geminin is stabilized due to APC/C ubiquitin ligase complex inhibition, ensuring the inhibition of pre-replicative complex formation. However, mitotic regulation of geminin has hitherto not been described. Here we show that Aurora-A phosphorylates geminin on Thr25 during M phase, and this event induces geminin stabilization by preventing its APC/C ubiquitin ligase complex-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCF(Skp2)-mediated degradation of Cdt1 to ensure pre-replicative complex formation in the ensuing S phase. The Aurora-A-geminin-Cdt1 axis therefore represents a critical regulator of proper DNA replication.
    Nature Communications 01/2013; 4:1885. · 10.74 Impact Factor
  • Source
    The Annals of Dentistry of the University of Malaya. 01/2013; 20(2):1-3.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Bovine lactoferrin (bLF) modulates the production of tumor necrosis factor (TNF)-α, and inhibits alveolar bone destruction associated with periodontitis. This study was designed to examine the effects of orally administered liposomal bLF (LbLF) on orthodontic force (OF)-induced alveolar bone remodeling during experimental tooth movement. Methods: Two groups of Wistar strain male rats were treated with either LbLF or the vehicle in drinking water 7 days before OF-application. Lipopolysaccharide (LPS) was injected into the gingival sulcus in half the rats in each group. Thus, 4 groups named OF, OF+LbLF, OF+LPS and OF+LPS+LbLF were established. Results: Orally administered LbLF significantly reduced apical migration of junctional epithelium observed in OF and OF+LPS. In OF+LPS, osteoclast number in the alveolar crestal area was increased by LPS-treatment, whereas osteoclast number was significantly reduced in OF+LPS+LbLF through suppression of TNF-α production. Meanwhile, osteoclastic induction in the middle part, mainly from OF-application, was not affected by LbLF administration. Moreover, inhibition of tooth movement was not induced by LbLF. Conclusions: Orally administered LbLF significantly inhibits LPS-induced alveolar bone resorption but not OF-induced bone remodeling. It is suggested that LbLF could be a potent therapeutic and preventive agent to control periodontal inflammation in patients with orthodontic treatment.
    Journal of Periodontology 11/2012; · 2.40 Impact Factor

Publication Stats

4k Citations
565.75 Total Impact Points

Institutions

  • 1989–2014
    • Hiroshima University
      • • Department of Oral and Maxillofacial Pathobiology
      • • Department of Orthodontics and Craniofacial Developmental Biology
      • • Department of Periodontal Medicine
      • • Faculty of Dentistry
      • • School of Dentistry
      Hirosima, Hiroshima, Japan
    • Al-Azhar University
      • Department of Oral Pathology
      Al Qāhirah, Al Qāhirah, Egypt
  • 2012–2013
    • The University of Tokushima
      Tokusima, Tokushima, Japan
    • Istanbul University
      • Department of Family Medicine (Cerrahpasa Faculty of Medicine)
      İstanbul, Istanbul, Turkey
  • 2009–2011
    • Prefectural University of Hiroshima
      Hirosima, Hiroshima, Japan
  • 2007
    • Tokyo Medical and Dental University
      Edo, Tōkyō, Japan
  • 2004
    • Osaka University
      • Department of Mechanical Science and Bioengineering
      Suika, Ōsaka, Japan
  • 2003
    • Nagasaki University
      • Graduate School of Biomedical Sciences
      Nagasaki-shi, Nagasaki-ken, Japan
  • 1997–2003
    • University of Michigan
      • School of Dentistry
      Ann Arbor, MI, United States
  • 2002
    • Keio University
      • Department of Dermatology
      Edo, Tōkyō, Japan
  • 2001
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1999
    • Peking University School of Stomatology
      Peping, Beijing, China
    • Sichuan University
      • West China School of Stomatology
      Chengdu, Sichuan Sheng, China