| 1. |
Kogo Takamiya, Akihito Yamamoto, Keiko Furukawa, Shuji Yamashiro, Masashi Shin, Masahiko Okada, Satoshi Fukumoto, Masashi Haraguchi, Naoki Takeda, Koichi Fujimura, Mihoko Sakae, Masao Kishikawa, Hiroshi Shiku, Koichi Furukawa, Shinichi Aizawa, Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.93.20.10662, Vol.93, No.20, pp.10662-10667, 1996.10, Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to play essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted β1,4-N- acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2,4.1.92) gone. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.. |
| 2. |
Akihito Yamamoto, Masashi Haraguchi, Shuji Yamashiro, Satoshi Fukumoto, Keiko Furukawa, Kogo Takamiya, Mitsuru Atsuta, Hiroshi Shiku, Koichi Furukawa, Heterogeneity in the expression pattern of two ganglioside synthase genes during mouse brain development, Journal of Neurochemistry, 10.1046/j.1471-4159.1996.66010026.x, Vol.66, No.1, pp.26-34, 1996.01, Gangliosides are synthesized by sequential catalytic reaction of multiple glycosyltransferases. GM2/GD2 synthase and GD3 synthase are key enzymes for ganglioside synthesis, because their relative activities regulate the main profiles of ganglioside expression. Mouse GD3 synthase (EC 2.4.99.8) cDNA was cloned by eukaryotic expression cloning, and its mRNA expression as well as that of GM2/GD2 synthase gene during the development of the mouse CNS was analyzed by using northern blotting, reverse transcription-polymerase chain reaction, and in situ hybridization. When brain tissue was analyzed as a whole mass, a typical pattern corresponding to the reported findings obtained by biochemical analyses was observed, i.e., high expression of GD3 synthase gene in the early stage and gradual increase of GM2/GD2 synthase gene expression in the late stage of the development. However, the results of in situ hybridization of these two genes revealed that the expression kinetics of these two genes were heterogeneous among various sites in the brain under development. These findings suggest that various expression patterns of the two genes reflect differences in the course of the development of individual sites, and also different ganglioside components are required in individual portions of the brain for development and maintenance of the function.. |
| 3. |
Effects of Ganglioside for regeneration of axotomized hypoglossal nerve in vivo. |
| 4. |
Satoshi Fukumoto, Akihito Yamamoto, Tomokazu Hasegawa, Kuniko Abe, Kogo Takamiya, Masahiko Okada, Zhao Jin Min, Keiko Furukawa, Hiroshi Miyazaki, Yoshiro Tsuji, George Goto, Misao Suzuki, Hiroshi Shiku, Koichi Furukawa, Genetic remodeling of gangliosides resulted in the enhanced reactions to the foreign substances in skin, Glycobiology, 10.1093/glycob/7.8.1111, Vol.7, No.8, pp.1111-1120, 1997.12, Several lines of transgenic mice with gangliosides GM2/GD2 synthase gene were established, and the expression levels of the transgene in brain, liver, spleen and thymus were analyzed by comparing with those in their litter mates. Among four tissues, brain and skin showed markedly high expression levels of the transgene in Northern blotting. Particularly, transgenic mice skin showed about 10-fold higher expression of GM2/GD2 synthase gene than the wild type mice skin. Therefore, alterations in the morphology, glycolipid components, and responses to the exogenous stimulations in the transgenic mice skin were examined. Gangliosides in the transgenic skin were dramatically converted from GM3 to GM1, whereas no morphological changes were observed. However, when skin flap test was performed with insertion of nylon membranes under the skin flaps, much stronger inflammatory reactions consisting of edema, marked thickness, and cell infiltration were observed in the transgenic mice compared with the wild type. Similar enhanced inflammatory reaction was also observed in the skin injected by silicon gel, and in the peritoneal reaction to the injected casein. Main cell population in these inflammatory reactions consisted of neutrophils, suggesting an increased sensitivity of neutrophils to chemotactic factors in the transgenic mice.. |
| 5. |
Hiroshi Miyazaki, Hiroshi Miyazaki, Satoshi Fukumoto, Satoshi Fukumoto, Masahiko Okada, Masahiko Okada, Tomokazu Hasegawa, Keiko Furukawa, Koichi Furukawa, Koichi Furukawa, Expression cloning of rat cDNA encoding UDP-galactose:G(D2) β1,3- galactosyltransferase that determines the expression of G(D1b)/G(M1)/G(A1), Journal of Biological Chemistry, 10.1074/jbc.272.40.24794, Vol.272, No.40, pp.24794-24799, 1997.10, Using an anti-G(D1b) monoclonal antibody, expression cloning of a cDNA for the β1,3-galactosyltransferase gene (EC 2.4.1.62) was performed. KF4C, mouse melanoma B16 transfected with polyoma T antigen gene, and G(M2)/G(D2) synthase cDNA was used as a recipient cell line for the cDNA library transfection. A cDNA clone of G(D3) synthase, pD3T-31 was co-transfected with a cDNA library prepared from rat brain RNA using the pcDNAI expression vector. The isolated cDNA clone pM1T-9 pre dieted a type II membrane protein with 4 amino acids of cytoplasmic domain, 21 amino acids of transmembrane region, and a large catalytic domain with 346 amino acids. Introduction of the cDNA clone into a mouse melanoma line B16 previously transfected with a G(M2)/G(D2) synthase gene resulted in the neo-synthesis of G(M1). Co- transfection of the cell line with pM1T-9 and a G(D3) synthase cDNA resulted in the expression of G(D1b) as well as G(M1). Moreover, introduction of pM1T- 9 into L cell (lacking G(MS) synthase), previously transfected with G(M2)/G(D2) synthase gene, resulted in the definite expression of asialo- G(M1). These results indicated that G(D1b)/G(M1)/G(A1) synthases were identical, as previously suggested based on enzymological analysis. In Northern blots of the β1,3- galactosyltransferase gene with total RNA from various rat tissues, a 1.6-kilobase mRNA was strongly expressed in spleen, thymus, kidney, and testis. However, the expression level of the gene in the adult brain tissue was not especially high. On the other hand, this gene was expressed at high levels in the rat brain of embryonal day 12, and reached a peak at around birth, then fell to low level in the adult brain.. |
| 6. |
Effect of Knoop Hardness on the Post-Irradiation Color Changes of Light Cured Composite Resin. |
| 7. |
Kogo Takamiya, Akihito Yamamoto, Keiko Furukawa, Jinmin Zhao, Satoshi Fukumoto, Shuji Yamashiro, Masahiko Okada, Masashi Haraguchi, Masashi Shin, Masao Kishikawa, Hiroshi Shiku, Shinichi Aizawa, Koichi Furukawa, Complex gangliosides are essential in spermatogenesis of mice: Possible roles in the transport of testosterone, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.95.21.12147, Vol.95, No.21, pp.12147-12152, 1998.10, Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4.1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous fluid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.. |
| 8. |
Satoshi Fukumoto, Aya Tuneoka, Yoko Kamasaki, Yumiko Hosoya, George Goto, Transposition of mesial and distal aspects of maxillary first molars: Case report, Journal of Clinical Pediatric Dentistry, Vol.23, No.3, pp.265-269, 1999.03, Congenital absence of one or more teeth, hypodontia, is the most common developmental anomaly and is often accompanied by the presence of other tooth anomalies. In this case two Japanese sisters have several congenitally missing primary and permanent teeth and morphological abnormalities of maxillary first molars. One sister has transposition of mesial and distal aspects of a maxillary first molar, whose cusps display a normal shape. Another sister has maxillary first molars, which look like maxillary second molars. Mesio-distally shift of teeth is a very rare anomaly making this particular case important to analyze the teeth formation and development.. |
| 9. |
Satoshi Fukumoto, Aya Tuneoka, Yoko Kamasaki, Yumiko Hosoya, George Goto, Transposition of mesial and distal aspects of maxillary first molars: Case report, Journal of Clinical Pediatric Dentistry, Vol.23, No.3, pp.265-269, 1999.03, Congenital absence of one or more teeth, hypodontia, is the most common developmental anomaly and is often accompanied by the presence of other tooth anomalies. In this case two Japanese sisters have several congenitally missing primary and permanent teeth and morphological abnormalities of maxillary first molars. One sister has transposition of mesial and distal aspects of a maxillary first molar, whose cusps display a normal shape. Another sister has maxillary first molars, which look like maxillary second molars. Mesio-distally shift of teeth is a very rare anomaly making this particular case important to analyze the teeth formation and development.. |
| 10. |
Michi Ichiro Itoh, Satoshi Fukumoto, Nobuyuki Baba, Yoshiro Kuga, Akio Mizuno, Koichi Furukawa, Prevention of the death of the rat axotomized hypoglossal nerve and promotion of its regeneration by bovine brain gangliosides, Glycobiology, 10.1093/glycob/9.11.1247, Vol.9, No.11, pp.1247-1252, 1999.11, We have examined the time course of the neuronal death and regeneration of rat axotomized hypoglossal nerve with various conditions of the nerve resection, and established a useful system to measure neurotrophic activities of bioactive substances. In this system, neuronal death can be evaluated by counting surviving neurons in the nucleus of hypoglossal neuron at the brain stem, and the degree of the regeneration can be measured by counting horseradish peroxidase-positive cells at the same region after injection of horseradish peroxidase into tongue. Using this system, the effects of brain gangliosides on rat hypoglossal nerve regeneration following 5 mm transection were examined. The addition of a ganglioside mixture from bovine brain as well as the autograft strongly prevented the death of neurons and promoted the regeneration of the lesioned nerve at 10 weeks after the operation. Further analyses on the dose effects and injection sites of gangliosides were performed. Although the mechanisms of the neurotrophic effects of the gangliosides are unknown, the therapeutic application of gangliosides for neuronal degeneration is a promising approach.. |
| 11. |
Tetsuya Okajima, Satoshi Fukumoto, Satoshi Fukumoto, Hiroshi Miyazaki, Hideharu Ishida, Makoto Kiso, Keiko Furukawa, Takeshi Urano, Koichi Furukawa, Koichi Furukawa, Molecular cloning of a novel α2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids, Journal of Biological Chemistry, 10.1074/jbc.274.17.11479, Vol.274, No.17, pp.11479-11486, 1999.04, A novel member of the human CMP-NeuAc:β-galactoside α2,3- sialyltransferase (ST) subfamily, designated ST3Gal VI, was identified based on BLAST analysis of expressed sequence tags, and a cDNA clone was isolated from a human melanoma line library. The sequence of ST3Gal VI encoded a type II membrane protein with 2 amino acids of cytoplasmic domain, 32 amino acids of transmembrane region, and a large catalytic domain with 297 amino acids; and showed homology to previously cloned ST3Gal III, ST3Gal IV, and ST3Gal V at 34, 38, and 33%, respectively. Extracts from L cells transfected with ST3Gal VI cDNA in a expression vector and a fusion protein with protein A showed an enzyme activity of α2,3-sialyltransferase toward Galβ1,4GlcNAc structure on glycoproteins and glycolipids. In contrast to ST3Gal III and ST3Gal IV, this enzyme exhibited restricted substrate specificity, i.e. it utilized Galβ1, 4GlcNAc on glycoproteins, and neolactotetraosylceramide and neolactohexaosylceramide, but not lactotetraosylceramide, lactosylceramide, or asialo-GM1. Consequently, these data indicated that this enzyme is involved in the synthesis of sialyl-paragloboside, a precursor of sialyl- Lewis X determinant.. |
| 12. |
Tetsuya Okajima, Satoshi Fukumoto, Satoshi Fukumoto, Hiromi Ito, Makoto Kiso, Yoshio Hirabayashi, Takeshi Urano, Keiko Furukawa, Koichi Furukawa, Koichi Furukawa, Molecular cloning of brain-specific GD1α synthase (ST6GalNAc V) containing CAG/glutamine repeats, Journal of Biological Chemistry, 10.1074/jbc.274.43.30557, Vol.274, No.43, pp.30557-30562, 1999.10, A novel member of the mouse CMP-NeuAc: β-N-acetyl-galactosaminide α2,6-sialyltransferase (ST6GalNAc) subfamily, designated ST6GalNAc V, was identified by BLAST analysis of expressed sequence tags. The sequence of the longest cDNA clone of ST6GalNAc V encoded a type II membrane protein with 8 amino acids comprising the cytoplasmic domain, 21 amino acids comprising the transmembrane region, and 306 amino acids comprising the catalytic domain. The predicted amino acid sequence showed homology to the previously cloned ST6GalNAc III and IV, with common amino acid sequences in sialyl motifs L and S among these three enzymes. Eleven CAG repeats were found in the stem region. A fusion protein with protein A and extracts from L cells transfected with ST6GalNAc V in a expression vector showed enzyme activity of α2,6- sialyltransferase almost exclusively for GM1b, but not toward glycoproteins. Sialidase treatment and thin layer chromatography immunostaining revealed that the product was GD1α Northern blotting revealed that three transcripts of the gene were expressed specifically in brain tissues. It is concluded that this enzyme is involved in the synthesis of GD1α in the nervous tissues, and the CAG repeats may have implications in neurodegenerative diseases.. |
| 13. |
Tetsuya Okajima, Satoshi Fukumoto, Keiko Furukawat, Takeshi Urano, Koichi Furukawa, Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene, Journal of Biological Chemistry, 10.1074/jbc.274.41.28841, Vol.274, No.41, pp.28841-28844, 1999.10, Progeroid type Ehlers-Danlos (E-D) syndrome was reported to be caused by defects in galactosyltransferase I (EC 2.4.1.133), which is involved in the synthesis of common linkage regions of proteoglycans. Recently, we isolated cDNA of the galactosyltransferase I (XGalT-1) (Okajima, T., Yoshida, K., Kondo, T., and Furukawa, K. (1999) J. Biol. Chem. 274, 22915-22918). Therefore, we analyzed mutations in this gene of a patient with progeroid type E-D syndrome by reverse transcription polymerase chain reaction and direct sequencing. Two changes of G and T to A and C at 186 and 206, respectively, were detected. Then, we determined the genomic DNA sequences encompassing the A186D and L206P mutations, revealing that the unaffected parents and two siblings were heterozygous for either one of the two different mutations and normal, while the patient had both of two different mutant genes. Enzymatic functions of cDNA clones of XGalT-1 containing the individual mutations were examined, elucidating that L206P clone completely lost the activity, while A186D retained ~50% or 10% of the activity when analyzed with extracts from cDNA transfectant cells or recombinant soluble enzymes, respectively. Moreover, L206P enzyme showed diffuse staining in the cytoplasm of transfectant cells, while the wild type or A186D clones showed Golgi pattern. These results indicated that the mutations in XCalT-1 were at least one of main molecular basis for progeroid type E-D syndrome.. |
| 14. |
Satoshi Fukumoto, Satoshi Fukumoto, Hiroshi Miyazaki, George Goto, Takeshi Urano, Keiko Furukawa, Koichi Furukawa, Koichi Furukawa, Expression cloning of mouse cDNA of CMP-NeuAc:lactosylceramide α2,3- sialyltransferase, an enzyme that initiates the synthesis of gangliosides, Journal of Biological Chemistry, 10.1074/jbc.274.14.9271, Vol.274, No.14, pp.9271-9276, 1999.04, Expression cloning of a cDNA for the α2,3-sialyltransferase (GM3 synthase) (EC 2.4.99.-) gene was performed using a GM3-lacking mouse fibroblast line L cell and anti-GM3 monoclonal antibody. Plasmids from a cDNA library generated with poly(A)+ RNA of a mouse fibrosarcoma line CMS5j and pdl3027 (polyoma T antigen) were co-transfected into L cells. The isolated cDNA clone pM3T-7 predicted a type II membrane protein with 13 amino acids of cytoplasmic domain, 17 amino acids of transmembrane region, and a large catalytic domain with 329 amino acids. Introduction of the cDNA clone into L cells resulted in the neo-synthesis of GM3 and high activity of α2,3- sialyltransferase. Among glycosphingolipids, only lactosylceramide showed significant activity as an acceptor, indicating that this gene product is a sialyltransferase specific for the synthesis of GM3. An amino acid sequence deduced from the cloned cDNA showed the typical sialyl motif with common features among α2,3-sialyltransferases. Among various mouse tissues, brain, liver, and testis showed relatively high expression of a 2.3-kilobase mRNA, whereas all tissues, more or less, expressed this gene.. |
| 15. |
Jinmin Zhao, Keiko Furukawa, Satoshi Fukumoto, Masahiko Okada, Heiko Furugen, Hiroshi Miyazaki, Kogo Takamiya, Shinichi Aizawa, Hiroshi Shiku, Toshifumi Matsuyama, Koichi Furukawa, Attenuation of interleukin 2 signal in the spleen cells of complex ganglioside-lacking mice, Journal of Biological Chemistry, 10.1074/jbc.274.20.13744, Vol.274, No.20, pp.13744-13747, 1999.05, T cell development and function in complex ganglioside-lacking (GM2/GD2 synthase gene-disrupted) mice were analyzed. GM1, asialo-GM1, and GD1b were representative gangliosides expressed on T cells of the wild type mice and completely deleted on those of the mutant mice. The sizes and cell numbers of the mutant mice spleen and thymus were significantly reduced. Spleen cells from the mutant mice showed clearly reduced proliferation compared with the wild type when stimulated by interleukin 2 (IL-2) but not when treated with concanavalin A or anti-CD3 cross-linking. Expression levels of IL-2 receptor α, β, and γ, were almost equivalent, and up-regulation of α chain after T cell activation was also similar between the mutant and wild type mice. Activation of JAK1, JAK3, and SAT5 after IL-2 treatment was reduced, and c- fos expression was delayed and reduced in the mutant spleen cells, suggesting that the IL-2 signal was attenuated in the mutant mice probably due to the modulation of IL-2 receptors by the lack of complex gangliosides.. |
| 16. |
Application of Magnetic Attachments as Retainers for Denture Type Appliances : For maxillary denture type appliance. |
| 17. |
T Okajima, S Fukumoto, H Ito, M Kiso, Y Hirabayashi, T Urano, K Furukawa, K Furukawa, Molecular cloning of brain-specific GD1 alpha synthase (ST6GalNAc V) containing CAG/glutamine repeats (vol 274, pg 30557, 1999), JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.275, No.2, p.1520, 2000.01. |
| 18. |
Yoshinao Kojima, Satoshi Fukumoto, Keiko Furukawa, Tetsuya Okajima, Joelle Wiels, Keiko Yokoyama, Yasuo Suzuk, Takeshi Urano, Michio Ohta, Koichi Furukawa, Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids, Journal of Biological Chemistry, 10.1074/jbc.M909620199, Vol.275, No.20, pp.15152-15156, 2000.05, The expression cloning of a cDNA for globotriaosylceramide (Gb3)/CD77 synthase (α1,4-galactosyltransferase) was achieved using an anti-Gb3 antibody and mouse L cells as a recipient cell line for the transfection. The isolated cDNA clone designated pVTR1 predicted a type II membrane protein with 19 amino acids of cytoplasmic domain, 26 amino acids of transmembrane region, and a catalytic domain with 308 amino acids. Introduction of the cDNA clone into L cells resulted in the neosynthesis of Gb3/CD77, and the extracts of the transfectant cells showed α1,4-galactosyltransferase activity only on lactosylceramide and galactosylceramide. In Northern blotting, a 2.3-kilobase mRNA was strongly expressed in heart, kidney, spleen, and placenta and weakly in colon, small intestine, and brain. Transfection of the cDNA into L cells resulted in the constitution of sensitivity to the apoptosis with Shiga-like toxins (verotoxins). Since Gb3/CD77 synthase initiates the synthesis of globo series glycolipids, the isolation of this cDNA will make possible further investigations into the function of its important series of glycolipids.. |
| 19. |
Satoshi Fukumoto, Tatsuro Mutoh, Tomokazu Hasegawa, Hiroshi Miyazaki, Masahiko Okada, George Goto, Keiko Furukawa, Takeshi Urano, Koichi Furukawa, GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation, Journal of Biological Chemistry, 10.1074/jbc.275.8.5832, Vol.275, No.8, pp.5832-5838, 2000.02, A rat pheochromocytoma cell line (PC12) transfected with ganglioside GD3 synthase gene showed a marked change in the ganglioside profile and enhanced proliferation and no response of neurite extension to nerve growth factor (NGF) stimulation. In these transfectant cells, a continuous phosphorylation of TrkA and the activation of ERK1/2 without NGF treatment were observed. Proliferation inhibition experiments with kinase inhibitors such as herbimycin A, K-252a, and PD98059 revealed that the enhanced proliferation was actually due to the activation of the Ras/MEK/ERK pathway. A TrkA dimer was detected in the GD3 synthase transfectant cells regardless of NGF treatment by crosslinking and immunoblotting. The increased expression of GD1b and GT1b in these transfectant cells might induce the conformational change of TrkA to form a dimer and to be activated continuously. These results may indicate regulatory roles of gangliosides in cell proliferation under physiological and malignant processes.. |
| 20. |
Koichi Furukawa, Kogo Takamiya, Masahiko Okada, Masahiro Inoue, Satoshi Fukumoto, Keiko Furukawa, Novel functions of complex carbohydrates elucidated by the mutant mice of glycosyltransferase genes, Biochimica et Biophysica Acta - General Subjects, 10.1016/S0304-4165(00)00185-9, Vol.1525, No.1-2, pp.1-12, 2001.02, Complex carbohydrates consist of carbohydrate moieties and protein or lipid portions, resulting in the formation of glycoproteins, proteoglycans or glycosphingolipids. The polymorphic carbohydrate structures are believed to contain profound biological implications which are important in cell-cell or cell-extracellular matrix interactions. A number of studies to delineate the roles of carbohydrates have been performed, and demonstrated definite changes in their profiles, cellular phenotypic changes or, sometimes, morphological and functional changes in tissues after modification of their structures. Recent successes in the isolation of glycosyltransferase genes and their modification enzyme genes has enabled clearer demonstrations of the roles of complex carbohydrates. In particular, genetic modification of glycosyltransferase genes in mice can elucidate the biological significances of their products in vivo. Here, we summarize recent advances in the understanding of the roles of complex carbohydrates provided from studies of gene knock-out mice of glycosyltransferase and modification enzyme genes focusing on novel functions which had not been expected. © 2001 Elsevier Science B.V.. |
| 21. |
T Iwamoto, S Fukumoto, K Kanaoka, E Sakai, M Shibata, E Fukumoto, J Inokuchi, K Takamiya, K Furukawa, K Furukawa, Y Kato, A Mizuno, Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276, No.49, pp.46031-46038, 2001.12, Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanoI (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappaB ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. D-PDMP also inhibited the phosphorylation. of the inhibitor of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappaB and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.. |
| 22. |
T Iwamoto, S Fukumoto, K Kanaoka, E Sakai, M Shibata, E Fukumoto, J Inokuchi, K Takamiya, K Furukawa, K Furukawa, Y Kato, A Mizuno, Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M104464200, Vol.276, No.49, pp.46031-46038, 2001.12, Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanoI (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappaB ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. D-PDMP also inhibited the phosphorylation. of the inhibitor of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappaB and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.. |
| 23. |
Tsutomu Iwamoto, Tsutomu Iwamoto, Satoshi Fukumoto, Kazuhiro Kanaoka, Eiko Sakai, Mitsue Shibata, Emiko Fukumoto, Emiko Fukumoto, Jin Ichi Inokuchi, Kogo Takamiya, Keiko Furukawa, Koichi Furukawa, Yuzo Kato, Akio Mizuno, Lactosylceramide Is Essential for the Osteoclastogenesis Mediated by Macrophage-Colony-stimulating Factor and Receptor Activator of Nuclear Factor-κB Ligand, Journal of Biological Chemistry, 10.1074/jbc.M104464200, Vol.276, No.49, pp.46031-46038, 2001.12, Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. D-PDMP also inhibited the phosphorylation of the inhibitor of nuclear factor-κB and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-κB and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.. |
| 24. |
S Yoshida, S Fukumoto, H Kawaguchi, S Sato, R Ueda, K Furukawa, Ganglioside G(D2) in small cell lung cancer cell lines: Enhancement of cell proliferation and mediation of apoptosis, CANCER RESEARCH, Vol.61, No.10, pp.4244-4252, 2001.05, Expression levels of gangliosides and glycosyltransferase genes responsible for their syntheses in human lung cancer cell lines and a normal bronchial epithelial cell line were analyzed. Both non-small cell lung cancers and small cell lung cancers (SCLCs) mainly expressed G(M2) and G(M1), whereas only SCLCs expressed b-series gangliosides, such as G(D2), G(D1b), and G(T1b). Accordingly, many SCLC cell lines showed up-regulation of the G(D3) synthase gene. Consequently, we introduced G(D3) synthase cDNA into a SCLC line with low expression of b-series gangliosides and analyzed the effects of newly expressed gangliosides on tumor phenotypes. The transfectant cells expressing high levels of G(D2) and G(D3) exhibited markedly increased growth rates and strongly enhanced invasion activities. Addition of anti-G(D2) monoclonal antibodies into the culture medium of these cells resulted in the marked growth suppression of G(D2)-expressing cell lines with reduced activation levels of mitogen-activated protein kinases but not of nonexpressants, suggesting that G(D2) plays important roles in cell proliferation. Moreover, G(D2)-expressing cells treated with anti-G(D2) antibodies showed features of apoptotic cell death at 30 min after addition of antibodies, i.e., shrinkage of cytoplasm, binding of Annexin V, and staining with propidium iodide, followed by DNA fragmentation. This G(D2)-mediated apoptosis was associated with caspase-3 activation and partly inhibited by a caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. The finding that anti-G(D2) antibodies suppressed the cell growth and induced apoptosis of SCLC cells strongly suggested the usefulness of G(D2) as a target for the therapy of disastrous cancer, although the precise mechanisms for apoptosis remain to be clarified.. |
| 25. |
Shoko Yoshida, Satoshi Fukumoto, Haruhiko Kawaguchi, Shigeki Sato, Ryuzo Ueda, Koichi Furukawa, Ganglioside GD2 in small cell lung cancer cell lines: Enhancement of cell proliferation and mediation of apoptosis, Cancer Research, Vol.61, No.10, pp.4244-4252, 2001.05, Expression levels of gangliosides and glycosyltransferase genes responsible for their syntheses in human lung cancer cell lines and a normal bronchial epithelial cell line were analyzed. Both non-small cell lung cancers and small cell lung cancers (SCLCs) mainly expressed GM2 and GM1, whereas only SCLCs expressed b-series gangliosides, such as GD2, GD1b, and GT1b. Accordingly, many SCLC cell lines showed up-regulation of the GD3 synthase gene. Consequently, we introduced GD3 synthase cDNA into a SCLC line with low expression of b-series gangliosides and analyzed the effects of newly expressed gangliosides on tumor phenotypes. The transfectant cells expressing high levels of GD2 and GD3 exhibited markedly increased growth rates and strongly enhanced invasion activities. Addition of anti-GD2 monoclonal antibodies into the culture medium of these cells resulted in the marked growth suppression of GD2-expressing cell lines with reduced activation levels of mitogen-activated protein kinases but not of nonexpressants, suggesting that GD2 plays important roles in cell proliferation. Moreover, GD2-expressing cells treated with anti-GD2 antibodies showed features of apoptotic cell death at 30 min after addition of antibodies, i.e., shrinkage of cytoplasm, binding of Annexin V, and staining with propidium iodide, followed by DNA fragmentation. This GD2-mediated apoptosis was associated with caspase-3 activation and partly inhibited by a caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. The finding that anti-GD2 antibodies suppressed the cell growth and induced apoptosis of SCLC cells strongly suggested the usefulness of GD2 as a target for the therapy of disastrous cancer, although the precise mechanisms for apoptosis remain to be clarified.. |
| 26. |
S Fukumoto, K Furukawa, G Goto, Expression of GD3 synthase gene in ameloblast during mouse tooth development, JOURNAL OF DENTAL RESEARCH, Vol.80, No.4, p.1334, 2001.04. |
| 27. |
M Okada, M Itoh, M Haraguchi, T Okajima, M Inoue, H Oishi, Y Matsuda, T Iwamoto, T Kawano, S Fukumoto, H Miyazaki, K Furukawa, S Aizawa, K Furukawa, b-series ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.C100395200, Vol.277, No.3, pp.1633-1636, 2002.01, The polymorphic carbohydrate structures of gangliosides play regulatory roles. In particular, b-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to be critical in various biological events such as adhesion, toxin binding, neurite extension, cell growth, and apoptosis. To clarify the physiological functions of b-series gangliosides in vivo, we have established a gene knockout mouse of GD3 synthase. Although all b-series structures were deleted in the mutant mice, they showed an almost complete nervous tissue morphology with no apparent abnormal behavior. Moreover, no differences in Fas-mediated apoptotic reaction of lymphocytes between wild type and the mutant mice were detected. However, the mutant mice exhibited clearly reduced regeneration of axotomized hypoglossal nerves compared with the wild type, suggesting that b-series gangliosides are more important in the repair rather than in the differentiation of the nervous system and apoptotic process induced via Fas.. |
| 28. |
M Okada, M Itoh, M Haraguchi, T Okajima, M Inoue, H Oishi, Y Matsuda, T Iwamoto, T Kawano, S Fukumoto, H Miyazaki, K Furukawa, S Aizawa, K Furukawa, b-series ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.C100395200, Vol.277, No.3, pp.1633-1636, 2002.01, The polymorphic carbohydrate structures of gangliosides play regulatory roles. In particular, b-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to be critical in various biological events such as adhesion, toxin binding, neurite extension, cell growth, and apoptosis. To clarify the physiological functions of b-series gangliosides in vivo, we have established a gene knockout mouse of GD3 synthase. Although all b-series structures were deleted in the mutant mice, they showed an almost complete nervous tissue morphology with no apparent abnormal behavior. Moreover, no differences in Fas-mediated apoptotic reaction of lymphocytes between wild type and the mutant mice were detected. However, the mutant mice exhibited clearly reduced regeneration of axotomized hypoglossal nerves compared with the wild type, suggesting that b-series gangliosides are more important in the repair rather than in the differentiation of the nervous system and apoptotic process induced via Fas.. |
| 29. |
MI Ito, S Fukumoto, T Iwamoto, K Kawano, A Mizuno, A Rokutanda, K Furukawa, Specificity of carbohydrate structure of gangliosides in the activity to regenerate the rat axotomized hypoglossal nerve., JOURNAL OF DENTAL RESEARCH, Vol.81, p.A457, 2002.03. |
| 30. |
Teruhiko Mitsuda, Keiko Furukawa, Satoshi Fukumoto, Hiroshi Miyazaki, Takeshi Urano, Koichi Furukawa, Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals, Journal of Biological Chemistry, 10.1074/jbc.M107756200, Vol.277, No.13, pp.11239-11246, 2002.03, To investigate the molecular mechanisms of gangliosides for the regulation of cell proliferation, Swiss 3T3 cells were transfected with GM2/GD2 synthase and GM1 synthase cDNAs, resulting in the establishment of GM1-expressing (GM1+) lines. Compared with the vector control (GM1-) cell lines, GM1+ cells exhibited reduced cell proliferation by stimulation with platelet-derived growth factor (PDGF). In accordance with the reduced cell growth, GM1+ cells showed earlier decreases in the phosphorylation levels of PDGF receptor and less activation of MAP kinases than GM1- cells. To analyze the effects of GM1 expression on the PDGF/PDGF receptor (PDGFR) signals, the glycolipid-enriched microdomain (GEM) was isolated and the following results were obtained. (i) PDGFR predominantly distributed in the non-GEM fraction in GM1+ cells, while it was present in both GEM and non-GEM fractions in GM1- cells. (ii) Activation of PDGFR as detected by anti-phosphotyrosine antibody occurred almost in parallel with existing amounts of PDGFR in each fraction. (iii) GM1 binds with PDGFR in GEM fractions. These findings suggested that GM1 regulates signals via PDGF/PDGFR by controlling the distribution of PDGFR in- and outside of GEM, and also interacting with PDGFR in the GEM fraction as a functional constituent of the microdomain.. |
| 31. |
Ho Hsiang Chen, Satoshi Fukumoto, Keiko Furukawa, Akimasa Nakao, Seiji Akiyama, Takeshi Urano, Koichi Furukawa, Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene, International Journal of Cancer, 10.1002/ijc.10797, Vol.103, No.2, pp.169-176, 2003.01, Ganglioside functions in tumor metastasis were analyzed by carbohydrate remodeling of a mouse Lewis lung cancer (subline P29) by introducing β1,4GalNAc-T cDNA. Although P29 was originally a low-metastatic subline in the s.c. injection system, it showed high potential in lung metastasis when i.v.-injected via the tail vein. Two lines of GM2+ transfectants showed markedly reduced metastatic potential to the lung compared to 2 control lines. However, cell proliferation rates and expression levels of various cell adhesion molecules, e.g., integrin family members, SLex and CD44, were essentially unchanged after transfection of the cDNA. Then, cell adhesion to fibronectin-coated dishes was examined, showing that GM2+ transfectants attached to the plates much more slowly than controls, suggesting functional modulation of integrins with newly expressed GM2. Phosphorylation of the FAK located at downstream of integrin molecules was markedly reduced in GM2+ transfectants, suggesting that GM2 suppressed cell adhesion signals via fibronectin-integrin interaction. © 2002 Wiley-Liss, Inc.. |
| 32. |
E Sakai, S Fukumoto, K Kanaoka, M Shibata, T Iwamoto, E Fukumoto, K Okamoto, Y Kato, Subcellular localization of the receptor activator of NF-KappaB and SRC kinase in detergent insoluble fractions of osteoclasts, BONE, Vol.32, No.5, p.S155, 2003.05. |
| 33. |
K. Kanaoka, S. Fukumoto, K. Yuasa, K. Okamoto, M. Shibata, E. Sakai, Y. Kato, T. Iwamoto, F. Hashimoto, N. Yoshida, Regulation of osteoclast survival and activation by glycosphingolipids., JOURNAL OF DENTAL RESEARCH, Vol.82, p.B358, 2003.06. |
| 34. |
T. Iwamoto, S. Fukumoto, S. Yanamoto, G. Kawasaki, I. Yoshitomi, A. Mizuno, Expression of receptor activator of nuclear factor-kappaB ligand (RANKL) in oral cancer cells., JOURNAL OF DENTAL RESEARCH, Vol.82, p.B161, 2003.06. |
| 35. |
E. Fukumoto, H. Sakai, S. Fukumoto, T. Yagi, O. Takagi, Y. Kato, Cadherin-related neuronal receptors in incisor development, Journal of Dental Research, 10.1177/154405910308200105, Vol.82, No.1, pp.17-22, 2003.01, Cadherins are cell adhesion molecules that are critical for tissue development. In this report, we identified members of the cadherin family cadherin-related neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is expressed in both these stages. In situ hybridization showed that strong expression of CNR1 is strong in the secretory stage, but reduced in the early phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA is expressed almost at the same levels in the secretory and in the early phase of the early-maturation stages but is absent in the late phase of the early-maturation stage. Both CNR1 and 5 mRNA are continuously expressed in odontoblasts. Immunohistology showed that CNR proteins are expressed in the secretory and early-maturation stages of ameloblasts, but no protein expression at the late-maturation stage was observed. CNR proteins were continuously expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial and mesenchymal cells through N-terminal domain EC1 in vitro. These results suggest that CNR1 and CNR5 may play an important role in enamel and dentin formation, probably through cell-cell and/or cell-matrix interactions.. |
| 36. |
Takashi Nakamura, Fernando Unda, Susana De-Vega, Arnaldo Vilaxa, Satoshi Fukumoto, Kenneth M. Yamada, Yoshihiko Yamada, The Krüppel-like Factor Epiprofin Is Expressed by Epithelium of Developing Teeth, Hair Follicles, and Limb Buds and Promotes Cell Proliferation, Journal of Biological Chemistry, 10.1074/jbc.M307502200, Vol.279, No.1, pp.626-634, 2004.01, We identified a cDNA clone for epiprofin, which is preferentially expressed in teeth, by differential hybridization using DNA microarrays from an embryonic day 19.5 mouse molar cDNA library. Sequence analysis revealed that this cDNA encodes a member of the Krüppel-like factor family containing three characteristic C2H2-type zinc finger motifs. The full-length cDNA was obtained by the 5′ Cap capture method. Except for its 5′-terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of Krüppel-like factor 14/Sp6 (specificity protein 6), which was previously identified in expressed sequence tag data bases and GenBank™ by an Sp1 zinc finger DNA-binding domain search (Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P. L., Van Vooren, P., Riviere, M., Szpirer, J., and Szpirer, C. (2000) Genomics 70, 93-101). This sequence difference is due to differences in the assignment of the location of exon 1. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating dental epithelium, differentiated odontoblast, and also hair follicle matrix epithelium. In addition, whole mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge in developing limbs and the posterior neuropore. Transfection of an epiprofin expression vector revealed that this molecule is localized in the nucleus and promotes cell proliferation. Thus, epiprofin is a highly cell- and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of teeth, hair follicles, and limbs that may function in the development of these tissues by regulating cell growth.. |
| 37. |
K Furukawa, M Nishio, T Mitsuda, S Fukumoto, K Furukawa, Differential regulation of biosignals with GM1 ganglioside in the membrane microdomains, GLYCOBIOLOGY, Vol.14, No.11, p.1140, 2004.11. |
| 38. |
唇顎口蓋裂患児における齲蝕罹患率と好発部位について. |
| 39. |
上顎永久犬歯の歯胚形成及び萠出方向について. |
| 40. |
上下左右乳臼歯部に低位乳歯を認めた遠位中間肢異形成症疑い患児の1症例. |
| 41. |
S. Aizawa, S. Aizawa, H. Miyasawa-Hori, K. Nakajo, J. Washio, H. Mayanagi, S. Fukumoto, N. Takahashi, N. Takahashi, Effects of α-amylase and its inhibitors on acid production from cooked starch by oral streptococci, Caries Research, 10.1159/000189703, Vol.43, No.1, pp.17-24, 2009.03, This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of α-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of α-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding α-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of α-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of α-amylase, the pH fell to 3.9-4.4 and the acid production rate was 0.61-0.92 μmol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, α-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of α-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. α-Amylase inhibitors and xylitol might moderate this activity. Copyright © 2009 S. Karger AG, Basel.. |
| 42. |
器官形成における転写因子エピプロフィンの機能. |
| 43. |
Aya Yamada, Tsutomu Iwamoto, Takashi Nakamura, Satoshi Fukumoto, Regulation of ameloblastin expression via gap junctional communication, FASEB JOURNAL, Vol.24, 2010.04. |
| 44. |
Tsutomu Iwamoto, Takashi Nakamura, Aya Yamada, Yoshihiko Yamada, Satoshi Fukumoto, Pannexin 3, a gap junction protein, Regulates Odontoblasts Differentiation, FASEB JOURNAL, Vol.24, 2010.04. |
| 45. |
Ryoko Miyamoto, Aya Yamada, Tsutomu Iwamoto, Takashi Nakamura, Satoshi Fukumoto, Expression of filamin-A during tooth development, FASEB JOURNAL, Vol.24, 2010.04. |
| 46. |
Takashi Nakamura, Kenji Yuasa, Lucia Jimenez, Fernando Unda, Eiki Koyama, Satoshi Fukumoto, Yoshihiko Yamada, Essential roles of zinc finger factor epiprofin in tooth development, FASEB JOURNAL, Vol.24, 2010.04. |
| 47. |
中村 卓史, 成瀬 正啓, 池内 友子, 新垣 真紀子, 福本 敏, 新規小分子化合物による骨芽細胞分化誘導, Journal of Oral Biosciences, Vol.53, No.Suppl., p.116, 2011.09. |
| 48. |
新規小分子化合物を用いた歯原性上皮細胞の増殖と分化制御. |
| 49. |
小児科医のための子どもの歯科 歯の再生. |
| 50. |
Tsutomu Iwamoto, Mariko Ono, Takashi Nakamura, Aya Yamada, Yoshihiko Yamada, Satoshi Fukumoto, Expression and Functional Roles of Pannexin 3 in Odontoblast Proliferation and Differentiation, FASEB JOURNAL, Vol.25, 2011.04. |
| 51. |
Takashi Nakamura, Satoshi Fukumoto, Yoshihiko Yamada, Diverse functions of Epiprofin in ectodermal organogenesis, FASEB JOURNAL, Vol.25, 2011.04. |
| 52. |
歯の発生におけるスフィンゴ糖脂質の役割. |
| 53. |
小児歯科臨床教育への3D映像技術の導入について. |
| 54. |
Takashi Nakamura, Yoshihiko Yamada, Satoshi Fukumoto, Review: The regulation of tooth development and morphogenesis, Interface Oral Health Science 2011, 10.1007/978-4-431-54070-0_3, pp.14-21, 2012.01, © Springer 2012. A variety of vertebrate organs, including teeth, begins their development by inductive sequential and reciprocal interactions between epithelium and mesenchyme. In tooth development, the interactions between ectodermal-derived epithelium and the cranial neural crest-derived mesenchyme regulate the shape, position, and size of the tooth crown with a functional cusp. During tooth development, many signaling molecules and transcription factors regulate tooth development and morphogenesis. Recently, we reported Epiprofin, an Sp transcription factor, is expressed during tooth development and exerts critical roles in dental epithelial differentiation and the determination of tooth number. In this review, we describe the expression pattern and functions of Epiprofin in tooth development.. |
| 55. |
Tsutomu Iwamoto, Mariko Ono, Makiko Arakaki, Takashi Nakamura, Aya Yamada, Satoshi Fukumoto, Pannexin 3, a gap junction protein, regulates chondrocyte differentiation in part through hemichannel activity, Interface Oral Health Science 2011, 10.1007/978-4-431-54070-0_100, pp.346-348, 2012.01, © Springer 2012. Gap junctional communications play a crucial role for organogenesis including cartilage development. Pannexin 3 (Panx3) belongs to the new member of the gap junction pannexin family. However, the expression and function of Panx3 have not been cleared. Here, we demonstrate that Panx3 is expressed in cartridge, and regulates chondrocyte differentiation in vitro cell culture. Our observations indicate that Panx3 plays a crucial role for the differentiation of chondrocyte, and suggest that Panx3 is a key molecule for cartilage development.. |
| 56. |
Hideji Komatsu, Motohide Ikawa, Keishiro Karita, Satoshi Fukumoto, Measurement of tissue oxygenation level in human lip, Interface Oral Health Science 2011, 10.1007/978-4-431-54070-0_30, pp.128-130, 2012.01, © Springer 2012. Kashima (Optics Laser Technol 35: 485-489, 2003) reported a method based on the Beer-Lambert law for measuring blood volume and its oxygenation in a small volume of tissue ( |
| 57. |
Y. Kamasaki, T. Nakamura, K. Yoshizaki, T. Iwamoto, A. Yamada, E. Fukumoto, Y. Maruya, K. Iwabuchi, K. Furukawa, T. Fujiwara, S. Fukumoto, Glycosphingolipids regulate ameloblastin expression in dental epithelial cells, Journal of Dental Research, 10.1177/0022034511424408, Vol.91, No.1, pp.78-83, 2012.01, Neurotrophin 4 (NT-4) and its receptors regulate the differentiation of ameloblasts in tooth development. Gangliosides, sialic acids that contain glycosphingolipids (GSLs), are involved in a variety of membrane-associated cell physiological functions such as ligand-receptor signal transmission. However, the expression patterns and functions of GSLs during tooth development remain unclear. In this study, we identified strong expressions of GM3 and LacCer in dental epithelium, which give rise to differentiation into enamel-secreting ameloblasts. Exogenous GM3 and LacCer in dental epithelial cells induced the expression of ameloblastin (Ambn), while it was also interesting that GM3 synergistically exerted enhancement of NT-4-mediated Ambn expression. In addition, consistently exogenous GM3 and LacCer in dental epithelial cells induced distinct activation of extracellular signal-regulated kinase 1/2 (ERK1/2), an event upstream of the expression of Ambn. Furthermore, depletion of GSLs from dental epithelial cells by D-threo-1-phenyl-2-decanoylamino-3- morpholino-1-propanol (D-PDMP) inhibited Ambn expression as well as phosphorylation of ERK1/2. In contrast, exogenous addition of GM3 or LacCer rescued the phosphorylation of ERK1/2 repressed by pre-treatment with D-PDMP. Taken together, these results suggest that GM3 and LacCer are essential for NT-4-mediated Ambn expression, and contribute to dental epithelial cell differentiation into ameloblasts. © 2012 International & American Associations for Dental Research.. |
| 58. |
Satoshi Fukumoto, Makiko Arakaki, Tsutomu Iwamoto, Aya Yamada, Ryoko Miyamoto, Masahiro Naruse, Takashi Nakamura, Epithelial cell lines in the field of dental research: Review, Interface Oral Health Science 2011, 10.1007/978-4-431-54070-0_97, pp.327-333, 2012.01, © Springer 2012. The interaction between the epithelium and mesenchyme induces specific molecular and cellular changes that lead to organogenesis. These interactions are particularly crucial during the initiation of the development of ectodermal organs, such as teeth, skin, hair, and mammary and prostate glands. The oral epithelium provides the initial signaling for neuronal crest-derived ectomesenchyme development, and then both tissues interact during tooth formation. Various transcription factors, growth factors, and extracellular matrices are expressed by enamel matrix-producing ameloblasts during tooth development. Dental epithelium was lost after tooth eruption in human. To analysis of dental cell proliferation and differentiation, we should use the dental epithelial cells from tooth germ, for example third molar, supernumerary tooth or continuous erupting rodent incisor. However, primary culture of dental epithelium has a limited number of cells and passage times. Because of these reasons, cell lines from dental tissue are useful to clear the molecular mechanism of these processes. Here we introduce cell lines from dental tissues, especially dental epithelium.. |
| 59. |
Hitomi Domon-Tawaraya, Kazuko Nakajo, Jumpei Washio, Satoshi Fukumoto, Nobuhiro Takahashi, Divalent cations enhance short-time fluoride exposure-induced inhibition on acid production by Streptococcus mutans, Interface Oral Health Science 2011, 10.1007/978-4-431-54070-0_47, pp.178-180, 2012.01, © Springer 2012. This study aimed to evaluate the effects of divalent cations on the short-time fluoride exposure induced-inhibition of the pH fall ability of Streptococcus mutans. In the presence of divalent cations, short-time fluoride exposure enhanced the inhibition of pH fall by S. mutans, probably due to the fluoride bound to bacterial cell via cations. Thus, it is suggested that the pre-rinse with divalent cations increases fluoride retention to plaque bacteria and subsequently enhances fluoride inhibition on acid production by dental plaque in vivo.. |
| 60. |
歯胚形成におけるビタミンDの役割. |
| 61. |
歯科再生利用実現化を目指した新しい分子機能予測法開発. |
| 62. |
The influence of Sox21 as a novel ameloblast marker on tooth germ differentiation. |
| 63. |
小児歯科臨床教育へ向けた3D映像視聴に対するアンケート調査. |
| 64. |
Analysis of Connexin43-FGF10 signaling on salivary gland development. |
| 65. |
Regulation of dental epithelial cell proliferation and differentiation by laminin. |
| 66. |
S-PRGフイラー含有歯磨剤を用いたプラーク除去効果の比較試験. |
| 67. |
P-40 The effect of octacalcium phosphate (OCP) on the differentiation of dental epithelial cells
Dental epithelial cell line SF2 expresses ameloblastin after stimulation of BMP2 or NT-4. Ameloblastin is one of the enamel matrices, and important for dental epithelial cell differentiation from iPS cells co-culturing with SF2 cells. Octacalcium phosphate (OCP) has been recognized to have a stimulatory capacity on osteoblastic differentiation. We evaluated whether OCP promotes ameloblastic cell differentiation.. |
| 68. |
Takashi Nakamura, Masahiro Naruse, Tomoko Ikeuchi, Toshihisa Komori, Aya Yamada, Masahiro Iwamoto, Satoshi Fukumoto, Novel Compounds Mimic Hedgehog Activity and Promote Osteoblast Differentiation in C3H10T1/2 Cells and Osteoblastic Cells from Runx2-Deficient Mice, JOURNAL OF BONE AND MINERAL RESEARCH, Vol.28, 2013.02. |
| 69. |
Takashi Nakamura, Satoshi Fukumoto, Genetics of supernumerary tooth formation, Journal of Oral Biosciences, 10.1016/j.job.2013.06.006, Vol.55, No.4, pp.180-183, 2013.11, Tooth development is initiated with placode formation followed by thickening of the oral ectoderm-derived dental epithelium. The dental epithelium then undergoes invagination into the dental mesench-yme, which is derived from the cranial neural crest. The subsequent reciprocal interactions between the dental epithelium and mesenchyme, involving a variety of molecules, are important for tooth morphogenesis, as well as for regulation of tooth number. Recent analyses of mouse mutants have provided important insights into the mechanisms underlying tooth development, including supernumerary tooth formation. In this review, we have discussed the molecular basis for the regulation of tooth number and supernumerary tooth formation.© 2013 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.. |
| 70. |
M. Sakano, K. Otsu, N. Fujiwara, S. Fukumoto, A. Yamada, H. Harada, Cell dynamics in cervical loop epithelium during transition from crown to root: Implications for Hertwig's epithelial root sheath formation, Journal of Periodontal Research, 10.1111/jre.12003, Vol.48, No.2, pp.262-267, 2013.04, Background and Objective: Some clinical cases of hypoplastic tooth root are congenital. Because the formation of Hertwig's epithelial root sheath (HERS) is an important event for root development and growth, we have considered that understanding the HERS developmental mechanism contributes to elucidate the causal factors of the disease. To find integrant factors and phenomenon for HERS development and growth, we studied the proliferation and mobility of the cervical loop (CL). Material and Methods: We observed the cell movement of CL by the DiI labeling and organ culture system. To examine cell proliferation, we carried out immunostaining of CL and HERS using anti-Ki67 antibody. Cell motility in CL was observed by tooth germ slice organ culture using green fluorescent protein mouse. We also examined the expression of paxillin associated with cell movement. Results: Imaging using DiI labeling showed that, at the apex of CL, the epithelium elongated in tandem with the growth of outer enamel epithelium (OEE). Cell proliferation assay using Ki67 immunostaining showed that OEE divided more actively than inner enamel epithelium (IEE) at the onset of HERS formation. Live imaging suggested that mobility of the OEE and cells in the apex of CL were more active than in IEE. The expression of paxillin was observed strongly in OEE and the apex of CL. Conclusion: The more active growth and movement of OEE cells contributed to HERS formation after reduction of the growth of IEE. The expression pattern of paxillin was involved in the active movement of OEE and HERS. The results will contribute to understand the HERS formation mechanism and elucidate the cause of anomaly root. © 2012 John Wiley & Sons A/S.. |
| 71. |
Severe periodontitis in a patient with CD 18 deficiency. |
| 72. |
Tsutomu Iwamoto, Masaki Ishikawa, Mariko Ono, Takashi Nakamura, Satoshi Fukumoto, Yoshihiko Yamada, Biological roles of gap junction proteins in cartilage and bone development, Journal of Oral Biosciences, 10.1016/j.job.2012.12.001, Vol.55, No.1, pp.29-33, 2013.02, Cell-cell and cell-matrix interactions are essential for cell differentiation, function, and maintenance of skeletal tissue. Gap junction proteins, composed of connexin (Cx) and pannexin (Panx) families, mediate these interactions and play an important role in cell-cell communications. Cx and Panx share similar protein structures, but have evolved differently. The Panx family was initially identified by its sequence homology to the invertebrate gap junction innexin family. The Panx family comprises three members, Panx1, 2, and 3. Panx1 is expressed in many organs, such as the eyes, thyroid, prostate, kidneys, and liver, but its expression is especially strong in the central nervous system. Similarly, Panx2 is expressed mainly in the central nervous system. Panx3 is expressed predominantly in skeletal tissues, including cartilage and bone. In this review, we describe the expression and functions of Cxs and Panx3 in cartilage and bone. © 2013 Japanese Association for Oral Biology.. |
| 73. |
新規転写因子エピプロフィンによる副甲状腺ホルモン発現制御. |
| 74. |
中村 卓史, 福本 敏, エピプロフィンによる上皮細胞増殖制御機構(Molecular mechanism of Epiprofin in epithelial cell proliferation), Journal of Oral Biosciences Supplement, Vol.2014, p.123, 2014.09. |
| 75. |
インドネシア人3姉弟へ行った齲蝕治療及び齲蝕予防処置について. |
| 76. |
「新う蝕予防」― S-PRG 技術を応用した新しい齲蝕予防の概念―. |
| 77. |
S-PRGフィラー含有歯磨剤のプラーク除去効果について. |
| 78. |
Satoshi Fukumoto, Takashi Nakamura, Aya Yamada, Makiko Arakaki, Kan Saito, Juan Xu, Emiko Fukumoto, Yoshihiko Yamada, New insights into the functions of enamel matrices in calcified tissues, Japanese Dental Science Review, 10.1016/j.jdsr.2014.01.001, Vol.50, No.2, pp.47-54, 2014.05, Ameloblasts secrete enamel matrix proteins, including amelogenin, ameloblastin, enamelin, amelotin, and Apin/odontogenic ameloblast-associated protein (Apin/ODAM). Amelogenin is the major protein component of the enamel matrix. Amelogenin, ameloblastin, and enamelin are expressed during the secretory stage of ameloblast, while amelotin and Apin/ODAM are expressed during the maturation. Amelogenin and ameloblastin are also expressed in osteoblasts, and they regulate bone formation. In addition, recent studies show the importance of protein-protein interactions between enamel matrix components for enamel formation. In a mouse model mimicking a mutation of the amelogenin gene in amelogenesis imperfect (AI) in humans, the mutated amelogenin forms a complex with ameloblastin, which accumulates in the endoplasmic reticulum/Golgi apparatus and causes ameloblast dysfunction resulting in AI phenotypes. Ameloblastin is a cell adhesion molecule that regulates cell proliferation. It inhibits odontogenic tumor formation and regulates osteoblast differentiation through binding to CD63. Amelotin interacts with Apin/ODAM, but not ameloblastin, while Apin/ODAM binds to ameloblastin. These interactions may be important for enamel mineralization during amelogenesis. The enamel matrix genes are clustered on human chromosome 4 except for the amelogenin genes located on the sex chromosomes. Genes for these enamel matrix proteins evolved from a common ancestral gene encoding secretory calcium-binding phosphoprotein. © 2014 Japanese Association for Dental Science.. |
| 79. |
飲水時に引き起こされた乳歯の完全脱臼の2例. |
| 80. |
発生から考えた歯の再生. |
| 81. |
健康長寿を育む歯学教育コンソーシアム―東北大学の取り組み―. |
| 82. |
P-5 Effect of three-dimensional culture on ameloblast differentiation of dental epithelial cells
Dental epithelial cell line SF2 expresses ameloblastin after stimulation of BMP2 or NT-4. Ameloblastin is one of the enamel matrices, and important for dental epithelial cell differentiation from iPS cells co-culturing with SF2 cells. A 3D cell culture mimics the functions of living tissues compared to a monolayer culture. In this study, SF2 cells were cultured three-dimensionally and evaluated for its differentiation into ameloblasts compared to the monolayer culture. We found that the expression of markers of ameloblast differentiation of SF2 cells was promoted by 3D culture compared to that of monolayer culture.. |
| 83. |
Mayu Suzuki, Aya Yamada, Kan Saito, Ryoko Hino, Yu Sugawara, Mariko Ono, Masahiro Naruse, Makiko Arakaki, Satoshi Fukumoto, Application of a tooth-surface coating material containing pre-reacted glass-ionomer fillers for caries prevention, Pediatric Dental Journal, 10.1016/j.pdj.2015.08.003, Vol.25, No.3, pp.72-78, 2015.12, © 2015 The Japanese Society of Pediatric Dentistry. Purpose Several methods have been used to prevent dental caries, including fluoride application to strengthen teeth and promote remineralization and the use of sealants to fill pits and fissures in pediatric dentistry. However, none of these methods alone can be considered a perfect preventive treatment. For caries prevention, we evaluated pre-reacted glass-ionomer (PRG) Barrier Coat (Shofu Inc., Kyoto, Japan), a tooth-surface coating material developed using PRG technology that contains high levels of controlled-release fluoride. Methods The tooth-surface coating material was applied clinically as a new method of preventing dental caries. Its effect on plaque adhesion, along with its preventive effect on dental caries was investigated in actual cases treated in a pediatric dentistry department of a university hospital. Results PRG Barrier Coat was shown to have suitable adhesive strength and to be a safe material that does not fracture the adherend. Actual ion release and acid buffering were confirmed, and when clinically applied, continuous fluoride release and recharge occurred, as did the release of the other ions. This suggests that this material promoted dentin remineralization, suppressed plaque adherence, and had a preventive effect on dental caries. Conclusion This material promoted enamel remineralization, suppressed plaque adherence, and had a preventive effect on dental caries. These results suggest that this coating material is appropriate for young children at high risk of dental caries.. |
| 84. |
A-4 Influence of three-dimensional culture on differentiation of dental epithelial cells into ameloblasts
Dental epithelial cell line SF2 cells secrete some enamel proteins stimulated by BMP-2 and NT-4. Three-dimensional cell culture can mimic natural condition in the body compared to monolayer culture. In this study, we investigated whether three dimensional culture affects the differentiation of SF2 cells into ameloblasts compared to the monolayer culture.. |
| 85. |
組織再生に関わる基礎研究基盤の現状 エピプロフィンは歯原性上皮細胞のエナメル芽細胞系への誘導と分化を制御する多機能制御因子である. |
| 86. |
当科における過剰歯に関しての臨床統計的検討. |
| 87. |
健康長寿を育む歯学教育コンソーシアム―東北大学の取り組み 第2報―. |
| 88. |
【歯の細胞生物学】 エナメル芽細胞の分化制御機構
歯の最外層は,エナメルと呼ばれる高度に石灰化した組織で覆われている.エナメルは,皮膚や毛,爪などと同様の外胚葉系上皮細胞が分化したエナメル芽細胞によって形成される,生体で唯一上皮組織が産生する硬組織である.エナメル芽細胞は,器官形成期のみ限定的に存在している細胞で,歯の発生が完了すると退縮上皮となり消滅してしまう.このため,すべての永久歯の発生が完了した成人では,エナメル芽細胞は存在せず,損傷したエナメル質を修復できる生物学的プロセスはなく,損傷はすべて不可逆性である.歯の再生医療を考えた場合,エナメル質形成に不可欠なエナメル芽細胞をどのように調達するかが課題となる.本稿では,歯原性上皮細胞からエナメル芽細胞へと分化する制御機構について述べるとともに,最近患児の増加が伝えられているくる病と臼歯切歯エナメル質形成不全症との関連について紹介する.(著者抄録). |
| 89. |
S‐PRGフィラーの研磨材としての評価. |
| 90. |
東日本大震災の被災地域における自己記入型食事調査票を用いた間食指導について. |
| 91. |
健康長寿を育む歯学教育コンソーシアム―東北大学の取り組み 第3報―. |
| 92. |
Issei Saitoh, Satoshi Fukumoto, Yoko Iwase, Haruaki Hayasaki, Youichi Yamasaki, Unilateral open-bite caused by an impacted primary molar with ankylosis: A case report, Pediatric Dental Journal, 10.1016/j.pdj.2017.04.001, Vol.27, No.3, pp.147-152, 2017.12, © 2017 Japanese Society of Pediatric Dentistry Management of the developing dentition and occlusion performs early and healthy oral optimization by diagnosing and treating their malocclusion and dysfunction in optimal period. We treated a posterior open-bite triggered by an impacted tooth with ankylosis. Her second primary molar was impacted with ankylosis of the buccal roots. She usually had her tongue thrust against her right posterior teeth. Timely and actively accelerated eruption of her second premolar was produced by extracting her second primary molar with fenestration. Her result shows the importance of improving oral habits and treating the submersion in the optimal period during early growth.. |
| 93. |
Takahisa Anada, Mayu Tadaki, Yukari Shiwaku, Takashi Nakamura, Masanori Nakamura, Masaru Kojima, Tatsuo Arai, Satoshi Fukumoto, Osamu Suzuki, The effect of three-dimensional culture on the ameloblastic differentiation of dental epithelial cells, 2016 International Symposium on Micro-NanoMechatronics and Human Science, MHS 2016, 10.1109/MHS.2016.7824173, 2017.01, © 2016 IEEE. We have developed three-dimensional (3D) cell culture devices. The present study investigated that the effect of 3D culture of rat incisor-derived dental epithelial cells on their differentiation into ameloblast-like cells.. |
| 94. |
Y. Tanaka, H. Nagashima, K. Bando, L. Lu, A. Ozaki, Y. Morita, S. Fukumoto, N. Ishii, S. Sugawara, Oral CD103 - CD11b + classical dendritic cells present sublingual antigen and induce Foxp3 + regulatory T cells in draining lymph nodes, Mucosal Immunology, 10.1038/mi.2016.46, Vol.10, No.1, pp.79-90, 2017.01, © 2017 Society for Mucosal Immunology. Sublingual immunotherapy (SLIT) is a safe and efficient treatment for type 1 allergies; however, the underlying immunological mechanisms, particularly the phenotype of oral antigen-presenting cells (APCs) responsible for the induction of regulatory T (Treg) cells, remain unclear. We show here that the sublingual application of ovalbumin (OVA) induced antigen-specific Foxp3 + Treg cells in draining submandibular lymph nodes (ManLNs). Oral APCs were classified into macrophages, classical dendritic cells (cDCs), and Langerhans cells by flow cytometry. A major subset of oral cDCs with the CD103 - CD11b + phenotype showed retinoic acid (RA)-producing activity and converted naive CD4 + T cells to Foxp3 + Treg cells in a transforming growth factor-β- and RA-dependent manner in vitro. In the ManLNs, migratory CD103 - CD11b + cDCs also showed RA-producing activity. After the sublingual application of fluorescent OVA, fluorescence was detected in oral macrophages in tissues, followed by migratory CD103 - CD11b + cDCs in ManLNs and migratory CD103 - CD11b + cDCs were the main APCs responsible for the induction of sublingual antigen-specific Treg cells. The transfer of OVA-SLIT-induced Treg cells suppressed the OVA-induced hypersensitivity response. These results suggest that oral CD103 - CD11b + cDCs transport sublingual antigens to draining ManLNs and induce antigen-specific Foxp3 + Treg cells, and, thus, provide a rationale for developing cDC-based therapeutic approaches in SLIT.. |
| 95. |
歯冠・歯根長を制御する新規歯胚形態制御因子の同定と機能解明. |
| 96. |
新規basic-helix-loop-helix転写因子AmeloDは歯原性上皮細胞の遊走能を制御し歯胚形態形成に関与する. |
| 97. |
健康長寿を育む歯学教育コンソーシアム―東北大学の取り組み 第4報―. |
| 98. |
Koji Hirayama, Takashi Hanada, Ryoko Hino, Kan Saito, Mayu Kobayashi, Makiko Arakaki, Yuta Chiba, Norihiko Nakamura, Takeshi Sakurai, Tsutomu Iwamoto, Satoshi Fukumoto, Aya Yamada, Material properties on enamel and fissure of surface pre-reacted glass-ionomer filler-containing dental sealant, Pediatric Dental Journal, 10.1016/j.pdj.2018.05.001, Vol.28, No.2, pp.87-95, 2018.08, © 2018 Japanese Society of Pediatric Dentistry Purpose: In pediatric dentistry, sealants have been used to prevent caries. Due to its material properties such as fluoride-releasing ability and physical strength, surface pre-reacted glass (S-PRG) filler is added primarily to resin-based dental materials for clinical use. In this study, we investigated the properties of S-PRG filler containing sealant. Methods: Before using sealant, the primer was applied to extracted bovine incisors. Scanning electron microscopy (SEM) observation revealed that the primer treatment caused no structural changes of enamel surface, unlike conventional phosphoric acid etching. Further, shear bond strength test was performed to measure the initial strength and durability after thermal cycling. Bond strength of S-PRG filler containing sealant was comparable to those of other sealants even though the former does not involve phosphoric acid etching. In addition, after treating the enamel surface with the primer or phosphoric acid, it showed excellent flowability in the primer group compared to phosphoric acid treatment. Results: SEM observation showed that the sealant sealed the enamel surface as it migrated to reach the deep areas of the fissures. When the marginal sealing ability of the sealant was evaluated based on dye penetration, no dye penetration in the marginal region was observed in any specimens. In addition, measurement of the pH of an acid solution containing a cured specimen of the sealant containing S-PRG filler showed that the solution's pH became more alkaline as the immersion time increased. Conclusion: These findings suggest that the sealant is an extremely effective material for preventing caries.. |
| 99. |
内エナメル上皮の新規マーカーAmeloDの転写制御機構解明. |
| 100. |
Yukinori Tanaka, Satoshi Fukumoto, Shunji Sugawara, Mechanisms underlying the induction of regulatory T cells by sublingual immunotherapy, Journal of Oral Biosciences, 10.1016/j.job.2019.02.001, Vol.61, No.2, pp.73-77, 2019.06, © 2019 Japanese Association for Oral Biology Background: Sublingual immunotherapy (SLIT) is used for the treatment of type 1 allergies, such as allergic rhinitis. SLIT leads to tolerance against allergens possibly via the redirection of allergen-specific T helper 2 cells to T helper 1 cells and the generation of peripheral regulatory T (Treg) cells. However, the detailed mechanisms remain unclear. Systemic tolerance to orally administered antigens (oral tolerance) has been extensively investigated. Recent studies have recognized the central role of Treg cells and classical dendritic cells (cDCs) in oral tolerance development. Highlight: This review focuses on recent advances in the understanding of the underlying mechanisms of SLIT compared with those of oral tolerance. The sublingual administration of soluble protein antigens has been reported to induce antigen-specific Treg cells in oral mucosa-draining submandibular lymph nodes in mice. The generation of Treg cells is critical for SLIT efficacy because the transfer of SLIT-induced Treg cells confers tolerance against the antigens. A large number of oral cDCs with the CD103−CD11b+ phenotype exert retinoic acid-producing activity and convert naïve CD4+ T cells into Foxp3+ Treg cells in vitro in a transforming growth factor-β-dependent and retinoic acid-dependent manner. Oral CD103−CD11b+ cDCs transport sublingual antigens to submandibular lymph nodes and induce antigen-specific Treg cells. Sublingual antigens enter the mucosa most likely by crossing the sublingual ductal epithelium and are captured by oral antigen-presenting cells, especially macrophages. Conclusion: Oral CD103−CD11b+ cDCs are specialized for the induction of Treg cells in mice; thus, targeting their human counterpart may enhance the therapeutic effects of SLIT.. |
| 101. |
Fukumoto S., Yamada A., Fukumoto E., Yuasa K., Yoshizaki K., Iwamoto T., Nonaka K., Glycolipids regulate ameloblast differentiation, J Oral Biosci., ４９（２）１１３－１１９, 2007.03. |
| 102. |
Fukumoto S., Yamada A., Nonaka K., Yamada Y., Essential roles of ameloblastin in maintaining ameloblast differentiation and enamel formation., Cells Tissues Organs., 181（3-4）,189-195, 2006.04. |
| 103. |
Fukumoto S., Iwamoto T., Sakai E., Yuasa K., Fukumoto E., Yamada A., Hasegawa T., Nonaka K., Kato Y., Current topics in pharmacological research on bone metabolism: osteoclast differentiation regulated by glycosphingolipids., J Pharmacol Sci, 2006.03. |
| 104. |
Fukumoto S., Yamada Y., Extracellular matrix regurates tooth morphogenesis, Connect Tissue Res. 2005;46(4-5):220-6, 2005.08. |
