徳島大学 / 教育研究者総覧 --- 長谷川智一

専門分野

○	歯学 (Dentistry)

研究テーマ

○	歯根吸収, 再生医学

著書・論文

著書:

1.	長谷川智一, 田中光郎, 帖佐直幸, 浅川剛吉, 角田初恵 : 乳歯および永久歯歯根膜由来間葉系幹細胞による血管新生誘導および歯周組織再生法の開発, 2013年4月.
2.	長谷川智一 : 乳歯由来不死化歯根膜細胞株の樹立, 2011年10月.

学術論文(審査論文):

1.	Anrizandy Narwidina, Aya Miyazaki, Kokoro Iwata, Rika Kurogoushi, Asuna Sugimoto, Yasusei Kudo, Keita Kawarabayashi, Yoshihito Yamakawa, Yuki Akazawa, Takamasa Kitamura, Hiroshi Nakagawa, Kimiko Ueda Yamaguchi, Tomokazu Hasegawa, Keigo Yoshizaki, Satoshi Fukumoto, Akihito Yamamoto, Naozumi Ishimaru, Tomonori Iwasaki and Tsutomu Iwamoto : Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression., Biochemical and Biophysical Research Communications, Vol.650, 47-54, 2023. (要約) Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation. (キーワード) Homeodomain Proteins / Transcription Factors / Odontoblasts / Genes, Homeobox / 細胞分化 (cell differentiation) / 細胞増殖·分化 (cell proliferation and differentiation) (徳島大学機関リポジトリ) ● Metadata: 118052 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbrc.2023.02.004 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36773339 ● Search Scopus @ Elsevier (PMID): 36773339 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2023.02.004 (徳島大学機関リポジトリ: 118052, DOI: 10.1016/j.bbrc.2023.02.004, PubMed: 36773339)
2.	黒厚子璃佳, 岩田こころ, 中川弘, 長谷川智一, 上田(山口) 公子, 北村尚正, 赤澤友基, 杉本明日菜, 河原林啓太, 宮嵜彩, 尼寺理恵, 藤島史帆, 岩﨑智憲, 岩本勉 : 当科における5年間の障害児・有病児の初診時実態調査, 小児歯科学雑誌, Vol.60, No.1, 20-27, 2022年. (要約) 障害児や有病児への理解の深まりから社会環境や福祉制度の整備が進みつつあるが，障害や全身疾患をもつ児が地域において疾病予防も含めた歯科医療を受けられる環境がいまだ十分にあるとは言えず，実情に応じた環境整備が求められる．そこで，今回，平成25年度から平成29年度に当科を受診した児のうち障害児・有病児の5年間の初診時実態調査を行い，過去に当科で行った調査と比較し，近年の変化を検討した．初診患者1,301名のうち，障害児・有病児の割合は49 (キーワード) う蝕先天奇形口蓋裂口唇裂障害者歯科医療発達障害染色体異常小児歯科医療慢性疾患患者歯科医療病院歯科診療部門紹介と相談年齢因子徳島県実態調査地域差ヒト小児(6∼12) 男女歯学
3.	Takeyoshi Asakawa, Atsushi Yamada, Masumi Kugino, Tomokazu Hasegawa, Kentaro Yoshimura, Kiyohito Sasa, Mitsuhiro Kinoshita, Masakazu Nitta, Karin Nagata, Tomomi Sugiyama, Ryutaro Kamijo and Takahiro Funatsu : Establishment of Downs syndrome periodontal ligament cells by transfection with SV40T-Ag and hTERT, Human Cell, Vol.35, No.1, 379-383, 2022. (要約) Down's syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down's syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) and Down's syndrome patient (STPDLDS) samples. Primary cultured periodontal ligament cells obtained from a healthy subject (pPDL) had a limited number of population doublings (< 40), while STPDL and STPDLDS cells continued to grow with more than 80 population doublings. Primary cultured periodontal ligament cells obtained from the patient showed a chromosome pattern characteristic of Down's syndrome with trisomy 21, whereas STPDLDS samples showed a large number of abnormal chromosomes in those results. Gene expression analysis revealed that expression of DSCR-1 in STPDLDS is greater than that in STPDL. These results suggest that the newly established STPDLDS cell line may be a useful tool for study of periodontal disease in Down's syndrome patients. (キーワード) Antigens, Polyomavirus Transforming / Cell Line / DNA-Binding Proteins / Down Syndrome / Gene Expression / Healthy Volunteers / Humans / Male / Middle Aged / Muscle Proteins / Peptide Fragments / Periodontal Diseases / Periodontal Ligament / Telomerase / Transfection (徳島大学機関リポジトリ) ● Metadata: 118955 (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s13577-021-00621-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34590290 ● Search Scopus @ Elsevier (PMID): 34590290 ● Search Scopus @ Elsevier (DOI): 10.1007/s13577-021-00621-0 (徳島大学機関リポジトリ: 118955, DOI: 10.1007/s13577-021-00621-0, PubMed: 34590290)
4.	Rika Kurogoushi, Tomokazu Hasegawa, Yuki Akazawa, Kokoro Iwata, Asuna Sugimoto, Kimiko Ueda Yamaguchi, Aya Miyazaki, Anrizandy Narwidina, Keita Kawarabayashi, Takamasa Kitamura, Hiroshi Nakagawa, Tomonori Iwasaki and Tsutomu Iwamoto : Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells, Experimental and Therapeutic Medicine, Vol.22, No.6, 1356, 2021. (要約) The regulation of the mesenchymal stem cell (MSC) programming mechanism promises great success in regenerative medicine. Tissue regeneration has been associated not only with the differentiation of MSCs, but also with the microenvironment of the stem cell niche that involves various cytokines and immune cells in the tissue regeneration site. In the present study, fibroblast growth factor 2 (FGF2), the principal growth factor for tooth development, dental pulp homeostasis and dentin repair, was reported to affect the expression of cytokines in human dental pulp-derived MSCs. FGF2 significantly inhibited the expression of chemokine C-C motif ligand 11 (CCL11) in a time- and dose-dependent manner in the SDP11 human dental pulp-derived MSC line. This inhibition was diminished following treatment with the AZD4547 FGF receptor (FGFR) inhibitor, indicating that FGF2 negatively regulated the expression of CCL11 in SDP11 cells. Furthermore, FGF2 activated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in SDP11 cells. The mechanism of the FGFR-downstream signaling pathway was then studied using the SB203580, U0126 and SP600125 inhibitors for p38 MAPK, ERK1/2, and JNK, respectively. Interestingly, only treatment with SP600125 blocked the FGF2-mediated suppression of CCL11. The present results suggested that FGF2 regulated the expression of cytokines and suppressed the expression of CCL11 via the JNK signaling pathway in human dental pulp-derived MSCs. The present findings could provide important insights into the association of FGF2 and CCL11 in dental tissue regeneration therapy. (徳島大学機関リポジトリ) ● Metadata: 117039 (出版サイトへのリンク) ● Publication site (DOI): 10.3892/etm.2021.10791 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34659502 ● Search Scopus @ Elsevier (PMID): 34659502 ● Search Scopus @ Elsevier (DOI): 10.3892/etm.2021.10791 (徳島大学機関リポジトリ: 117039, DOI: 10.3892/etm.2021.10791, PubMed: 34659502)
5.	岩田こころ, 黒厚子璃佳, 杉本明日菜, 藤島史帆, 赤澤友基, 河原林啓太, 宮嵜彩, 北村尚正, 尼寺理恵, 上田(山口) 公子, 中川弘, 長谷川智一, 岩本勉 : 当科における初診患者の実態調査∼平成における30年間の変遷∼, 小児歯科学雑誌, Vol.59, No.1, 8-13, 2021年. (要約) <p>2019年4月末日をもって平成時代が終わり，令和時代が幕を開けた．平成の約30年間は経済成長の低迷，晩婚化・少子化の加速，一方で高度化する情報通信技術等，小児を取り巻く環境は，昭和時代から急速に変化しさまざまな領域で二極化が顕在化してきた側面もある．われわれ小児歯科医は，社会環境・家庭環境などの変化が子供の発育に及ぼす影響や問題を的確に読み取り，対応と支援を考えなければならない．そこで，平成元年から平成30年を初期(平成元年度∼5年度)，中期(平成9年度∼13年度)，後期(平成25年度∼29年度)の各5年間で区切り，15年間の計5,982人を対象に当科に来院した初診患者の調査・分析を行った．</p><p>その結果，初診患者数は，年少人口の減少に伴い初期2,477人から後期1,301人と減少した．男女比は，各時期ともに概ね1:1であった．年齢は，いずれも学童期が約40%と最も多く，年齢構成に大きな変化はみられなかった．主訴は，各時期ともに齲蝕が最も多いが，初期の44%から後期には27%と減少した．紹介状を持参した児の割合は，初期の23%から後期は83.3%に増加し，障害児・有病児の割合が初期13.8%から後期33%に増加した．初期に比べ，主訴は多様化し，かかりつけ歯科医院と大学病院の機能分化が進んでいることが明らかとなった．今後は，さらに医科歯科連携の重要性が高まることが示唆された．</p> (キーワード) 実態調査 / 初診患者 / 平成 / 小児歯科 / Survey of actual state / New patients / Heisei / Pediatric dentistry (出版サイトへのリンク) ● Publication site (DOI): 10.11411/jspd.59.1_8 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390854139452228096 ● Search Scopus @ Elsevier (DOI): 10.11411/jspd.59.1_8 (DOI: 10.11411/jspd.59.1_8, CiNii: 1390854139452228096)
6.	Aya Miyazaki, Asuna Sugimoto, Keigo Yoshizaki, Keita Kawarabayashi, Kokoro Iwata, Rika Kurogohshi, Takamasa Kitamura, Kunihiro Otsuka, Tomokazu Hasegawa, Yuki Akazawa, Satoshi Fukumoto, Naozumi Ishimaru and Tsutomu Iwamoto : Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1, Scientific Reports, Vol.9, No.1, 14762, 2019. (要約) Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type mechanosensitive ion channel component 1 (PIEZO1) is a primary mechanosensing receptor for odontoblast differentiation through coordination of the WNT expression and ciliogenesis. In stem cells from human exfoliated deciduous teeth (SHED), HP significantly promoted calcium deposition as well as the expression of odontogenic marker genes, PANX3 and DSPP, and WNT related-genes including WNT5b and WNT16, whereas HP inhibited cell proliferation and enhanced primary cilia expression. WNT signaling inhibitor XAV939 and primary cilia inhibitor chloral hydrate blocked the HP-induced calcium deposition. The PIEZO1 activator Yoda1 inhibited cell proliferation but induced ciliogenesis and WNT16 expression. Interestingly, HP and Yoda1 promoted nuclear translocation of RUNX2, whereas siRNA-mediated silencing of PIEZO1 decreased HP-induced nuclear translocation of RUNX2. Taken together, these results suggest that PIEZO1 functions as a mechanotransducer that connects HP signal to the intracellular signalings during odontoblast differentiation. (徳島大学機関リポジトリ) ● Metadata: 114667 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-019-51381-9 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31611621 ● Search Scopus @ Elsevier (PMID): 31611621 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-019-51381-9 (徳島大学機関リポジトリ: 114667, DOI: 10.1038/s41598-019-51381-9, PubMed: 31611621)
7.	Kimiko Ueda Yamaguchi, Yuki Akazawa, Kawarabayashi Keita, Asuna Sugimoto, Hiroshi Nakagawa, miyazaki aya, Weih Falk, Kurogoushi Rika, Iwata Kokoro, Takamasa Kitamura, Yamada Aya, Tomokazu Hasegawa, Fukumoto Satoshi and Tsutomu Iwamoto : Combination of ions promotes cell migration via extracellular signalregulated kinase 1/2 signaling pathway in human gingival fibroblasts., Molecular Medicine Reports, Vol.19, No.6, 5039-5045, 2019. (要約) Wound healing is a dynamic process that involves highly coordinated cellular events, including proliferation and migration. Oral gingival fibroblasts serve a central role in maintaining oral mucosa homeostasis, and their functions include the coordination of physiological tissue repair. Recently, surface pre-reacted glass-ionomer (S-PRG) fillers have been widely applied in the field of dental materials for the prevention of dental caries, due to an excellent ability to release fluoride (F). In addition to F, S-PRG fillers are known to release several types of ions, including aluminum (Al), boron (B), sodium (Na), silicon (Si) and strontium (Sr). However, the influence of these ions on gingival fibroblasts remains unknown. The aim of the present study was to examine the effect of various concentrations of an S-PRG filler eluate on the growth and migration of gingival fibroblasts. The human gingival fibroblast cell line HGF-1 was treated with various dilutions of an eluent solution of S-PRG, which contained 32.0 ppm Al, 1,488.6 ppm B, 505.0 ppm Na, 12.9 ppm Si, 156.5 ppm Sr and 136.5 ppm F. Treatment with eluate at a dilution of 1:10,000 was observed to significantly promote the migration of HGF-1 cells. In addition, the current study evaluated the mechanism underlying the mediated cell migration by the S-PRG solution and revealed that it activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not of p38. Furthermore, treatment with a MEK inhibitor blocked the cell migration induced by the solution. Taken together, these results suggest that S-PRG fillers can stimulate HGF-1 cell migration via the ERK1/2 signaling pathway, indicating that a dental material containing this type of filler is useful for oral mucosa homeostasis and wound healing. (徳島大学機関リポジトリ) ● Metadata: 113289 (出版サイトへのリンク) ● Publication site (DOI): 10.3892/mmr.2019.10141 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31059063 ● Summary page in Scopus @ Elsevier: 2-s2.0-85066160258 (徳島大学機関リポジトリ: 113289, DOI: 10.3892/mmr.2019.10141, PubMed: 31059063, Elsevier: Scopus)
8.	Kifune Takashi, Ito Hisanori, Ishiyama Misa, Iwasa Satoko, Takei Hiroki, Tomokazu Hasegawa, Asano Masatake and Tetsuo Shirakawa : Hypoxia-induced up-regulation of angiogenic factors in immortalized human periodontal ligament fibroblasts, Journal of Oral Science, Vol.60, No.4, 519-525, 2018. (要約) Hypoxia induces complex cellular responses that are mediated by a key transcription factor, hypoxia-inducible factor-1 (HIF-1). HIF-1 promotes production of cytokines and angiogenic factors and contributes to recovery of injured tissues. In the present study, expressions of angiogenin (ANG) and vascular endothelial growth factor (VEGF), which are potent angiogenic factors in mammalian tissues, were examined in immortalized fibroblasts exposed to hypoxia. After 24 h of exposure to hypoxia, ANG and VEGF mRNAs expressions were significantly elevated in periodontal ligament (PDL) fibroblasts but not in embryonic fibroblasts. Hypoxia also increased productions of ANG and VEGF proteins in PDL fibroblasts. HIF-1α mRNA expression was not affected by hypoxia in either fibroblast, although HIF-1α protein expression was enhanced after exposure to hypoxia. Treatment of PDL fibroblasts with dimethyloxaloylglycine, a prolyl hydroxylase inhibitor that stabilizes the HIF-1α protein, significantly increased expressions of ANG and VEGF mRNAs under normoxia. This suggests that stabilization of HIF-1α is crucial for upregulation of ANG and VEGF in PDL fibroblasts. These results indicate that, under hypoxic conditions, HIF-1α upregulates synthesis of ANG and VEGF in PDL fibroblasts and promotes angiogenesis. (キーワード) Blotting, Western / Cell Line / Cells, Cultured / Cytokines / Fibroblasts / Fluorescent Antibody Technique / Humans / Hypoxia / Hypoxia-Inducible Factor 1 / Periodontal Ligament / RNA, Messenger / Real-Time Polymerase Chain Reaction / Ribonuclease, Pancreatic / Up-Regulation / Vascular Endothelial Growth Factor A (出版サイトへのリンク) ● Publication site (DOI): 10.2334/josnusd.17-0441 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30587686 ● Summary page in Scopus @ Elsevier: 2-s2.0-85059237563 (DOI: 10.2334/josnusd.17-0441, PubMed: 30587686, Elsevier: Scopus)
9.	Ito Hisanori, Kifune Takashi, Ishiyama Misa, Iwasa Satoko, Takei Hiroki, Tomokazu Hasegawa, Asano Masatake and Shirakawa Tetsuo : Effect of hypoxia on the expression of CCAAT/enhancer-binding protein β and receptor activator of NF-κB ligand in periodontal ligament cells, Journal of Oral Science, Vol.60, No.4, 544-551, 2018. (要約) Hypoxia after traumatic injuries to a tooth is one of the causes of subsequent root resorption. Inflammatory cytokines produced under hypoxic conditions are associated with root resorption, but the mechanism has not been fully understood. In this study, the role of hypoxia-inducible factor-1 (HIF-1) signaling in the regulation of CCAAT (cytosine-cytosine-adenosine-adenosine-thymidine)/enhancer-binding protein-β (C/EBPβ) and the receptor activator of nuclear factor kappa-B ligand (RANKL) expressions in immortalized human periodontal ligament (PDL) cells was investigated. PDL cells cultured under a hypoxic condition showed an increase in the expression of C/EBPβ and RANKL messenger RNAs (mRNAs), whereas the expression of osteoprotegerin and HIF-1α mRNAs was unaffected. Hypoxia had no effects on the secretion of interleukin (IL)-1β, IL-6, IL-8, IL-17A, tumor necrosis factor-alpha, macrophage migration inhibitory factor, monocyte chemoattractant protein-1, and macrophage colony-stimulating factor in the culture media. Treatment of the cells with dimethyloxaloylglycine, a competitive HIF prolyl hydroxylase inhibitor, significantly increased the expression of C/EBPβ and RANKL mRNAs. This suggested that the hypoxia-induced elevation of C/EBPβ and RANKL mRNAs was dependent on the HIF-1 activity. PDL cells transfected with a specific small interfering RNA designed to target the C/EBPβ gene showed a significant suppression of the RANKL mRNA. These findings indicated that C/EBPβ may play an important role in tooth root resorption via RANKL activation in hypoxia-exposed PDL cells. (キーワード) Amino Acids, Dicarboxylic / Blotting, Western / CCAAT-Enhancer-Binding Protein-beta / Cells, Cultured / Cytokines / Fluorescent Antibody Technique / Humans / Hypoxia / Periodontal Ligament / RANK Ligand / RNA, Messenger / RNA, Small Interfering / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction / Transfection (出版サイトへのリンク) ● Publication site (DOI): 10.2334/josnusd.17-0436 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30587688 ● Summary page in Scopus @ Elsevier: 2-s2.0-85059246642 (DOI: 10.2334/josnusd.17-0436, PubMed: 30587688, Elsevier: Scopus)
10.	Asuna Sugimoto, Aya Miyazaki, Keita Kawarabayashi, Masayuki Shono, Yuki Akazawa, Tomokazu Hasegawa, Kimiko Ueda Yamaguchi, Takamasa Kitamura, Yoshizaki keigo, Fukumoto Satoshi and Tsutomu Iwamoto : Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells, Scientific Reports, Vol.7, No.1, 17696, 2017. (要約) The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression. (徳島大学機関リポジトリ) ● Metadata: 112396 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-017-18089-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29255201 ● Summary page in Scopus @ Elsevier: 2-s2.0-85038567061 (徳島大学機関リポジトリ: 112396, DOI: 10.1038/s41598-017-18089-0, PubMed: 29255201, Elsevier: Scopus)
11.	Yoshitaka Yoshimura, Takashi Kikuiri, Tomokazu Hasegawa, Mino Matsuno, Hajime Minamikawa, Yoshiaki Deyama and Kuniaki Suzuki : How much medium do you use for cell culture? Medium volume influences mineralization and osteoclastogenesis in vitro, Molecular Medicine Reports, Vol.16, No.1, 429-434, 2017. (要約) Bone is maintained by a balance between bone formation and resorption. This remodeling is controlled by a wide variety of systemic and local factors including hormones, cytokines and mechanical stresses. The present in vitro study examined the impact of medium volume, using 0.4, 0.6, 0.8, 1.0, 1.5 and 2.0 ml/well in a 24-well plate, on the differentiation of osteoblasts and osteoclasts. There were no differences in the alkaline phosphatase activity of osteoblasts amongst the groups; however, the area of mineral deposition was decreased in a media volume-dependent manner. A co-culture of osteoblastic cells with bone marrow cells revealed a reduction in the total number of osteoclastic tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (≥2 nuclei), whereas the formation of large osteoclastic TRAP-positive multinuclear cells (≥8 nuclei) was increased, in a media volume-dependent manner. There were also no differences in receptor activator of nuclear factor-κB ligand mRNA and total osteoprotegerin (OPG) protein expression levels amongst the groups, however the concentration of OPG decreased in a media volume-dependent manner. In conclusion, the present study demonstrated that the suppression of mineralization in osteoblastic cells and the stimulation of osteoclast fusion are dependent on the medium volume, indicating that media volume is an important factor in in vitro cell culture systems. (出版サイトへのリンク) ● Publication site (DOI): 10.3892/mmr.2017.6611 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28535008 ● Search Scopus @ Elsevier (PMID): 28535008 ● Search Scopus @ Elsevier (DOI): 10.3892/mmr.2017.6611 (DOI: 10.3892/mmr.2017.6611, PubMed: 28535008)
12.	Nan Ma, Di Yang, Hirohiko Okamura, Jumpei Teramachi, Tomokazu Hasegawa, Lihong Qiu and Tatsuji Haneji : Involvement of interleukin23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis, Molecular Medicine Reports, Vol.15, No.2, 559-566, 2017. (要約) Periapical lesions are characterized by the destruction of periapical bone, and occur as a result of local inflammatory responses to root canal infection by microorganisms including Porphyromonas endodontalis (P. endodontalis). P. endodontalis and its primary virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical lesions and alveolar bone loss. Interleukin-23 (IL-23) is critical in the initiation and progression of periodontal disease via effects on peripheral bone metabolism. The present study investigated the expression of IL-23 in tissue where a periapical lesion was present, and the effect of P. endodontalis LPS on the expression of IL-23 in periodontal ligament (PDL) cells. Reverse transcription- quantitative polymerase chain reaction and immunohistochemistry revealed increased levels of IL-23 expression in tissue with periapical lesions compared with healthy PDL tissue. Treatment with P. endodontalis LPS increased the expression of IL-23 in the SH-9 human PDL cell line. BAY11-7082, a nuclear factor κB inhibitor, suppressed P. endodontalis LPS-induced IL-23 expression in SH-9 cells. Treatment of RAW264.7 cells with conditioned medium from P. endodontalis LPS-treated SH-9 cells promoted osteoclastogenesis. By contrast, RAW264.7 cells treated with conditioned medium from IL-23-knockdown SH-9 cells underwent reduced levels of osteoclastogenesis. The results of the present study indicated that the expression of IL-23 in PDL cells induced by P. endodontalis LPS treatment may be involved in the progression of periapical lesions via stimulation of the osteoclastogenesis process. (キーワード) Animals / Chromones / Humans / Immunohistochemistry / Interleukin-23 / Lipopolysaccharides / Mice / Morpholines / NF-kappa B / NFATC Transcription Factors / Nitriles / Osteoblasts / Osteogenesis / Periodontitis / Phosphatidylinositol 3-Kinases / Porphyromonas endodontalis / Proto-Oncogene Proteins c-fos / RANK Ligand / RAW 264.7 Cells / RNA Interference / RNA, Small Interfering / Sulfones (出版サイトへのリンク) ● Publication site (DOI): 10.3892/mmr.2016.6041 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28000855 ● Search Scopus @ Elsevier (PMID): 28000855 ● Search Scopus @ Elsevier (DOI): 10.3892/mmr.2016.6041 (DOI: 10.3892/mmr.2016.6041, PubMed: 28000855)
13.	Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuo, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki and Junichiro Iida : Release from optimal compressive force suppresses osteoclast differentiation, Molecular Medicine Reports, Vol.14, No.5, 4699-4705, 2016. (要約) Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts derived from RAW264.7 cells was counted, and gene expression associated with osteoclast differentiation and fusion in response to release from compressive force was evaluated by reverse transcription-quantitative polymerase chain reaction. Osteoclast number was increased by optimal compressive force application. On release from this force, osteoclast differentiation and fusion were suppressed. mRNA expression of NFATc1 was inhibited for 6 h subsequent to release from compressive force. mRNA expression of the other osteoclast-specific genes, TRAP, RANK, matrix metalloproteinase-9, cathepsin-K, chloride channel 7, ATPase H+ transporting vacuolar proton pump member I, dendritic cell-specific transmembrane protein and osteoclast stimulatory transmembrane protein (OC-STAMP) was significantly inhibited at 3 h following release from compressive force compared with control cells. These findings suggest that release from optimal compressive force suppresses osteoclast differentiation and fusion, which may be important for developing orthodontic treatments. (キーワード) Animals / Bone Resorption / Cell Differentiation / Cell Line / Cells, Cultured / Gene Expression Profiling / Gene Expression Regulation / Mice / Osteoclasts / Stress, Mechanical (出版サイトへのリンク) ● Publication site (DOI): 10.3892/mmr.2016.5801 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27748817 ● Search Scopus @ Elsevier (PMID): 27748817 ● Search Scopus @ Elsevier (DOI): 10.3892/mmr.2016.5801 (DOI: 10.3892/mmr.2016.5801, PubMed: 27748817)
14.	Takako Hayakawa, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Kenjiro Shibata, Yoshiaki Deyama, Kuniaki Suzuki and Junichiro Iida : Optimal compressive force accelerates osteoclastogenesis in RAW264.7 cells, Molecular Medicine Reports, Vol.12, No.4, 5879-5885, 2015. (要約) Mechanical stress produced by orthodontic forces is a factor in the remodeling of periodontal ligaments (PDLs) and alveolar bone. It has been reported that the expression of a number of cytokines associated with osteoclastogenesis is upregulated when compressive forces act on osteoblasts and PDL cells. The present study investigated the effects of compressive forces on the formation of osteoclasts from the macrophage cell line RAW264.7. Compressive forces on osteoclasts were exerted using layers of 3, 5, 7, 9 or 14 glass cover slips on the 4th day of culture for 24 h. The number of osteoclasts was determined by counting the number of cells positive for tartrate-resistant acid phosphatase staining. Osteoclastogenesis advanced rapidly on days four and five. The number of osteoclasts with >8 nuclei peaked when the force of 7 slips was applied, which was therefore regarded as the optimal compressive force. Alterations in the expression of osteoclast-associated genes are associated with changes in the differentiation and fusion of macrophages in response to compressive forces; therefore, osteoclast-associated genes were assessed by reverse transcription quantitative polymerase chain reaction in the present study. The mRNA expression of osteoclast-associated genes increased significantly after 3 h of optimal compression, whereas mRNA expression increased after 24 h in the control group. These findings suggested that osteoclastogenesis of macrophages was accelerated when an optimal compressive force was applied. (出版サイトへのリンク) ● Publication site (DOI): 10.3892/mmr.2015.4141 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26238100 ● Summary page in Scopus @ Elsevier: 2-s2.0-84940512325 (DOI: 10.3892/mmr.2015.4141, PubMed: 26238100, Elsevier: Scopus)
15.	Yuki Akazawa, Tomokazu Hasegawa, Yoshitaka Yoshimura, Naoyuki Chosa, Takeyoshi Asakawa, Kimiko Ueda Yamaguchi, Asuna Sugimoto, Takamasa Kitamura, Hiroshi Nakagawa, Akira Ishisaki and Tsutomu Iwamoto : Recruitment of mesenchymal stem cells by stromal cell-derived factor 1 in pulp cells from deciduous teeth, International Journal of Molecular Medicine, Vol.36, 442-448, 2015. (要約) Dental pulp cells (DPCs), including dental pulp (DP) stem cells, play a role in dentine repair under certain conditions caused by bacterial infections associated with caries, tooth fracture and injury. Mesenchymal stem cells (MSCs) have also been shown to be involved in this process of repair. However, the mechanisms through which MSCs are recruited to the DP have not yet been elucidated. Therefore, the aim of the present in vitro study was to investigate whether stromal cell-derived factor 1 (SDF1)-C-X-C chemokine receptor type 4 (CXCR4) signaling is involved in tissue repair in the DP of deciduous teeth. A single-cell clone from DPCs (SDP11) and UE7T-13 cells were used as pulp cells and MSCs, respectively. The MG-63 and HuO9 cells, two osteosarcoma cell lines, were used as positive control cells. Reverse transcription polymerase chain reaction (RT-PCR) revealed that all cell lines (SDP11, UE7T-13 MG-63 and HuO9) were positive for both SDF1 and CXCR4 mRNA expression. Moreover, immunocytochemical analysis indicated that SDF1 and CXCR4 proteins were expressed in the SDP11 and UE7T-13 cells. SDF1 was also detected in the cell lysates (CLs) and conditioned medium (CM) collected from the SDP11 and UE7T-13 cells, and AMD3100, a specific antagonist of CXCR4, inhibited the migration of the UE7T-13 cells; this migration was induced by treatment with CM, which was collected from the SDP11 cells. In addition, real-time PCR showed that the expression of SDF1 in the SDP11 cells was inhibited by treatment with 20 ng/ml fibroblast growth factor (FGF)-2, and exposure to AZD4547, an inhibitor of the FGF receptor, blocked this inhibition. Collectively, these data suggest that SDF1 produced by DP plays an important role in homeostasis, repair and regeneration via the recruitment of MSCs. (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2015.2247 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26082290 ● Summary page in Scopus @ Elsevier: 2-s2.0-84934271560 (DOI: 10.3892/ijmm.2015.2247, PubMed: 26082290, Elsevier: Scopus)
16.	Tomokazu Hasegawa, Yuki Akazawa, Takamasa Kitamura, Asuna Sugimoto, Kimiko Ueda Yamaguchi and Tsutomu Iwamoto : Dental findings and management in a child with hypomelanosis of Ito, Pediatric Dental Journal, Vol.24, No.3, 173-177, 2014. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.pdj.2014.08.002 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84938485288 (DOI: 10.1016/j.pdj.2014.08.002, Elsevier: Scopus)
17.	Emiko Aomatsu, Noriko Takahashi, Shunsuke Sawada, Naoto Okubo, Tomokazu Hasegawa, Masayuki Taira, Hiroyuki Miura, Akira Ishisaki and Naoyuki Chosa : Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells, Scientific Reports, Vol.4, 3652, 2014. (要約) Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intriguingly, SCRG1 maintained stem cell marker expression (Oct-4 and CD271/LNGFR) and the potentials of self-renewal, migration, and osteogenic differentiation, even at high passage numbers. Thus, the novel SCRG1/BST1 axis determines the fate of hMSCs by regulating their kinetic and differentiation potentials. Our findings provide a new perspective on methods for ex vivo expansion of hMSCs that maintain native stem cell potentials for bone-forming cell therapy. (キーワード) ADP-ribosyl Cyclase / Antigens, CD / Cell Differentiation / Cell Movement / Down-Regulation / Extracellular Signal-Regulated MAP Kinases / Focal Adhesion Protein-Tyrosine Kinases / GPI-Linked Proteins / Gene Expression Regulation, Developmental / Humans / JNK Mitogen-Activated Protein Kinases / Mesenchymal Stromal Cells / Nerve Tissue Proteins / Osteogenesis / Phosphatidylinositol 3-Kinases / Protein Binding / Protein Biosynthesis / Signal Transduction (出版サイトへのリンク) ● Publication site (DOI): 10.1038/srep03652 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24413464 ● Summary page in Scopus @ Elsevier: 2-s2.0-84892598136 (DOI: 10.1038/srep03652, PubMed: 24413464, Elsevier: Scopus)
18.	長谷川智一, 赤澤友基, 永井宏和, 北村尚正, 石丸直澄, 上田(山口) 公子, 中川弘, 郡由紀子, 山本愛美, 岩本勉 : 幼児期の小児の口蓋に発生した血管腫の1例, 小児歯科学雑誌, Vol.52, No.3, 448-453, 2014年. (要約) 血管腫は血管の増殖を特徴とする良性腫瘍であり，小児の顎口腔領域における良性腫瘍のなかでは比較的多く，軟組織腫瘍の中で最も多い．顎口腔領域に発生する本腫瘍は舌，口唇，歯肉，頬粘膜に好発し，口蓋に発生することは稀である．今回，われわれは，2 歳10 か月男児の口蓋に発生した血管腫を経験したので，その概要を報告する．患児は初診の約4 か月前に下顎部を打撲したため近医歯科を受診した．その際，上顎両側乳中切歯口蓋側歯肉の腫瘤を指摘され，単純性歯肉炎の診断下にプラークコントロールを受けていたが改善しないため当科を紹介された．初診時，切歯乳頭から上顎両側乳中切歯口蓋側歯肉にかけて大きさ10×8×5mm類円形で境界明瞭，暗赤色，表面不整，弾性軟の腫瘤を認め，上顎腫瘍と診断した．局所麻酔下に腫瘍切除術を施行した．病理組織学的診断は毛細血管腫であった．今後，再発に注意しながら，少なくとも永久歯交換まで厳重な経過観察が必要と考えられた． (キーワード) 血管腫 / 口蓋 / 幼児期 (出版サイトへのリンク) ● Publication site (DOI): 10.11411/jspd.52.3_448 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390282680495239168 ● Search Scopus @ Elsevier (DOI): 10.11411/jspd.52.3_448 (DOI: 10.11411/jspd.52.3_448, CiNii: 1390282680495239168)
19.	Jun Yokota, Jun Yokota, Shunsuke Sawada, Naoto Okubo, Noriko Takahashi, Tomokazu Hasegawa, Hisatomo Kondo and Akira Ishisaki : PDGF-induced PI3K-mediated signal enhances TGF--induced osteogenic differentiation of human mesenchymal stem cells in the TGF--activated MEK-dependent manner, International Journal of Molecular Medicine, Vol.33, No.3, 534-542, 2013. (要約) Transforming growth factor-β (TGF-β) is a critical regulator of osteogenic differentiation and the platelet-derived growth factor (PDGF) is a chemoattractant or mitogen of osteogenic mesenchymal cells. However, the combined effects of these regulators on the osteogenic differentiation of mesenchymal cells remains unknown. In this study, we investigated the effects of TGF-β and/or PDGF on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). The TGF-β-induced osteogenic differentiation of UE7T-13 cells, a bone marrow-derived hMSC line, was markedly enhanced by PDGF, although PDGF alone did not induce differentiation. TGF-β induced extracellular signal-regulated kinase (ERK) phosphorylation and PDGF induced Akt phosphorylation. In addition, the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor, U0126, suppressed the osteogenic differentiation induced by TGF-β alone. Moreover, U0126 completely suppressed the osteogenic differentiation synergistically induced by TGF-β and PDGF, whereas the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002, only partially suppressed this effect. These results suggest that the enhancement of TGF-β-induced osteogenic differentiation by PDGF-induced PI3K/Akt-mediated signaling depends on TGF-β-induced MEK activity. Thus, PDGF positively modulates the TGF-β-induced osteogenic differentiation of hMSCs through synergistic crosstalk between MEK- and PI3K/Akt-mediated signaling. (キーワード) Bone Marrow Cells / 細胞分化 (cell differentiation) / Elafin / Humans / MAP Kinase Kinase Kinases / Mesenchymal Stromal Cells / Osteogenesis / リン酸化 (phosphorylation) / Platelet-Derived Growth Factor / 情報伝達 (signal transduction) / Transforming Growth Factor beta (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2013.1606 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24378341 ● Summary page in Scopus @ Elsevier: 2-s2.0-84893868549 (DOI: 10.3892/ijmm.2013.1606, PubMed: 24378341, Elsevier: Scopus)
20.	Yuki Akazawa, Takamasa Kitamura, Yuri Fujihara, Yoshitaka Yoshimura, Masato Mitome and Tomokazu Hasegawa : Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus., International Journal of Molecular Medicine, Vol.31, No.2, 307-314, 2012. (要約) In this study, we examined the effect of forced mastication on neurogenesis in the hippocampal dentate gyrus (DG) of adult mice. Six-week-old mice were subjected to either a hard or normal diet for 13 weeks. They received a daily injection of bromodeoxyuridine (BrdU) for 12 consecutive days beginning at 14 weeks of age. The number of BrdU-positive cells in the DG was counted 1 day after and 5 weeks after the final BrdU injection. The number of BrdU-positive cells 1 day after injection did not differ between the 2 diet groups. However, the number of BrdU-positive cells in the group fed the hard diet was significantly increased 5 weeks after BrdU injection compared to the group fed the normal diet. The results of the Morris water maze test showed that mice fed a hard diet required significantly less time to reach the platform than the control mice when tested at 10 days. Moreover, mice in the group fed the hard diet spent significantly more time in the former platform area than the group fed the normal diet, indicating that hard diet feeding improved spatial memory compared to normal diet feeding. Real-time PCR analysis showed that the expression of glutamate receptor 1 mRNA was significantly increased in the group fed the hard diet compared with the group fed the normal diet. These results suggest that mastication increases the survival of adult neural stem cells in the hippocampal DG. (キーワード) Adult Stem Cells / Animals / Cell Proliferation / Cell Survival / Dentate Gyrus / Diet / Eating / Gene Expression Regulation, Developmental / Intercellular Signaling Peptides and Proteins / Mastication / Mice / Mice, Inbred C57BL / Nerve Growth Factors / Neural Stem Cells / Neurogenesis / RNA, Messenger (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2012.1217 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23254518 ● Summary page in Scopus @ Elsevier: 2-s2.0-84873182824 (DOI: 10.3892/ijmm.2012.1217, PubMed: 23254518, Elsevier: Scopus)
21.	Mariko Yoshida, Naoto Okubo, Naoyuki Chosa, Tomokazu Hasegawa, Miho Ibi, Masaharu Kamo, Seiko Kyakumoto and Akira Ishisaki : TGF-β-operated growth inhibition and translineage commitment into smooth muscle cells of periodontal ligament-derived endothelial progenitor cells through Smad- and p38 MAPK-dependent signals., International Journal of Biological Sciences, Vol.8, No.7, 1062-1074, 2012. (要約) The periodontal ligament (PDL) is a fibrous connective tissue that attaches the tooth to the alveolar bone. We previously demonstrated the ability of PDL fibroblast-like cells to construct an endothelial cell (EC) marker-positive blood vessel-like structure, indicating the potential of fibroblastic lineage cells in PDL tissue as precursors of endothelial progenitor cells (EPCs) to facilitate the construction of a vascular system around damaged PDL tissue. A vascular regeneration around PDL tissue needs proliferation of vascular progenitor cells and the subsequent differentiation of the cells. Transforming growth factor-β (TGF-β) is known as an inducer of endothelial-mesenchymal transition (EndMT), however, it remains to be clarified what kinds of TGF-β signals affect growth and mesenchymal differentiation of PDL-derived EPC-like fibroblastic cells. Here, we demonstrated that TGF-β1 not only suppressed the proliferation of the PDL-derived EPC-like fibroblastic cells, but also induced smooth muscle cell (SMC) markers expression in the cells. On the other hand, TGF-β1 stimulation suppressed EC marker expression. Intriguingly, overexpression of Smad7, an inhibitor for TGF-β-induced Smad-dependent signaling, suppressed the TGF-β1-induced growth inhibition and SMC markers expression, but did not the TGF-β1-induced downregulation of EC marker expression. In contrast, p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 suppressed the TGF-β1-induced downregulation of EC marker expression. In addition, the TGF-β1-induced SMC markers expression of the PDL-derived cells was reversed upon stimulation with fibroblast growth factor (FGF), suggesting that the TGF-β1 might not induce terminal SMC differentiation of the EPC-like fibroblastic cells. Thus, TGF-β1 not only negatively controls the growth of PDL-derived EPC-like fibroblastic cells via a Smad-dependent manner but also positively controls the SMC-differentiation of the cells possibly at the early stage of the translineage commitment via Smad- and p38 MAPK-dependent manners. (キーワード) Animals / Blotting, Western / Cell Proliferation / Cells, Cultured / Endothelial Cells / Fluorescent Antibody Technique / Myocytes, Smooth Muscle / Periodontal Ligament / Rats / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction / Smad Proteins / Stem Cells / Transforming Growth Factor beta / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.7150/ijbs.4488 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22949889 ● Search Scopus @ Elsevier (PMID): 22949889 ● Search Scopus @ Elsevier (DOI): 10.7150/ijbs.4488 (DOI: 10.7150/ijbs.4488, PubMed: 22949889)
22.	Tomokazu Hasegawa, Naoyuki Chosa, Takeyoshi Asakawa, Yoshitaka Yoshimura, Yuri Fujihara, Takamasa Kitamura, Mitsuro Tanaka, Akira Ishisaki and Masato Mitome : Differential effects of TGF-β1 and FGF-2 on SDF-1α expression in human periodontal ligament cells derived from deciduous teeth in vitro., International Journal of Molecular Medicine, Vol.30, No.1, 35-40, 2012. (要約) Stromal cell-derived factor (SDF)-1α has been reported to play a crucial role in stem cell homing and recruitment to injured sites. However, no information is available about its role in periodontal tissues. The aim of this in vitro study was to investigate the effects of basic fibroblast growth factor (FGF-2) and transforming growth factor (TGF)-β1 on SDF-1α expression in immortalized periodontal ligament (PDL) cells derived from deciduous teeth (SH9 cells). Real-time PCR and western blot analyses showed that SDF-1α mRNA expression in SH9 cells was markedly inhibited by FGF-2 treatment for 48 h. SU5402, which directly interacts with the catalytic domain of the FGF receptor 1 (FGFR1) and suppresses its phosphorylation, inhibited the FGF-2-related decrease in SDF-1α expression. These results suggest that FGF-2 signaling via the FGFR1 pathway inhibits SDF-1α expression. Conversely, SDF-1α expression in SH9 cells was increased by TGF-β1 treatment for 12 h. Western blot analysis showed that this treatment induced Smad2/3 phosphorylation. A time-course experiment showed that SDF-1α expression levels reached a maximum 12 h after the TGF-β1 treatment and returned to basal levels by 48 h. Real-time PCR analysis showed that Smad7 mRNA expression peaked by 6 h after TGF-β1 treatment. Since Smad7 siRNA downregulated Smad7 expression by approximately 2.5-fold compared with the negative control siRNA, the induction of SDF-1α expression was prolonged. Furthermore, treatment of SH9 cells with TGF-β1 for 12 h induced transwell migration of UE7T-13 cells, which are mesenchymal stem cells derived from human bone marrow. Therefore, SDF-1α may play an important role in stem and progenitor cell recruitment and homing to injured sites in the periodontal ligament, and regulation of SDF-1α expression may be a useful tool in cell-based therapy for periodontal tissue regeneration. (キーワード) Bone Marrow Cells / Cell Line / Cell Movement / Chemokine CXCL12 / Fibroblast Growth Factor 2 / Humans / Mesenchymal Stromal Cells / Periodontal Ligament / Phosphorylation / Pyrroles / RNA Interference / RNA, Messenger / RNA, Small Interfering / Receptors, Fibroblast Growth Factor / Smad2 Protein / Smad3 Protein / Smad7 Protein / Tooth, Deciduous / Transforming Growth Factor beta1 (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2012.957 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22469823 ● Search Scopus @ Elsevier (PMID): 22469823 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2012.957 (DOI: 10.3892/ijmm.2012.957, PubMed: 22469823)
23.	Keigo Abe, Yoshitaka Yoshimura, Yoshiaki Deyama, Tkashi Kikuiri, Tomokazu Hasegawa, Kanchu Tei, Hisashi shinoda, Kuniaki Suzuki and Yoshimasa Kitagawa : Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells., International Journal of Molecular Medicine, Vol.29, No.6, 1007-1015, 2012. (要約) Bisphosphonates are used as therapeutic agents for the management of osteoporosis and other bone diseases. However, the precise effects and mechanisms of bisphosphonates on osteoclastogenesis are unclear, as previous studies have reported contradictory findings and no studies have circumstantially assessed the effects of bisphosphonates on osteoclastogenesis. Therefore, the aim of this study was to determine the effects of bisphosphonates on osteoclastogenesis in RAW264.7 (RAW) cells. To examine the direct effects of bisphosphonates on osteoclast differentiation via receptor activator of nuclear factor-κB (RANK) ligand (RANKL), RAW cells were cultured with bisphosphonates. Addition of bisphosphonates to RAW cells led to a significant decrease in the number of osteoclasts and large osteoclasts (≥ 8 nuclei) in a bisphosphonate concentration-dependent and time-dependent manner. The cytotoxicity of non-nitrogen-containing bisphosphonates was specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells. Resorption activity was significantly diminished by treatment with bisphosphonates, thus confirming that bisphosphonates impair the absorptive activity of osteoclasts. We also investigated the effects of bisphosphonates on the mRNA expression of genes associated with osteoclastogenesis, osteoclast-specific markers and apoptosis-related genes using quantitative real-time PCR. The results suggest that bisphosphonates suppress osteoclast differentiation and infusion, and induce osteoclast apoptosis. With regard to osteoclast apoptosis induced by bisphosphonates, we further investigated the detection of DNA fragmentation and Caspase-Glo 3/7 assay. DNA fragmentation was confirmed after treatment with bisphosphonates, while caspase-3/7 activity increased significantly when compared with controls. In conclusion, bisphosphonates directly inhibited RANKL-stimulated osteoclast differentiation and fusion in RAW cells. It was confirmed that bisphosphonates impair osteoclast resorption activity and induce apoptosis. The effects of non-nitrogen-containing bisphosphonates were also specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells. (キーワード) Acid Phosphatase / Animals / Apoptosis / Biological Assay / Biological Markers / Caspase 3 / Caspase 7 / Cell Count / Cell Differentiation / Cell Line / DNA Fragmentation / Diphosphonates / Electrophoresis, Agar Gel / Gene Expression Regulation / Giant Cells / Isoenzymes / Mice / Osteoclasts / Osteogenesis / RNA, Messenger / Time Factors (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2012.952 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22447156 ● Search Scopus @ Elsevier (PMID): 22447156 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2012.952 (DOI: 10.3892/ijmm.2012.952, PubMed: 22447156)
24.	藤原百合, 赤澤友基, 北村尚正, 長谷川智一, 三留雅人 : 色素失調症により多数歯欠損が認められた症例, 障害者歯科, Vol.33, No.1, 74-79, 2012年. (キーワード) Bloch-Sulzberger syndrome / Congenital missing teeth / Infant denture (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1573387450569474944 (CiNii: 1573387450569474944)
25.	Takeyoshi Asakawa, Naoyuki Chosa, Yoshitaka Yoshimura, Asami Asakawa, Mitsuro Tanaka, Akira Ishisaki, Masato Mitome and Tomokazu Hasegawa : Fibroblast growth factor 2 inhibits the expression of stromal cell-derived factor 1 in periodontal ligament cells derived from human permanent teeth in vitro., International Journal of Molecular Medicine, Vol.29, No.4, 569-573, 2012. (要約) Although cells derived from periodontal ligament (PDL) tissue are reported to have stem cell-like activity and are speculated to play a crucial role for tissue healing and regeneration after injury or orthodontic treatment, mechanisms regulating their recruitment and activation remain unknown. Recently, stromal cell-derived factor 1α (SDF-1α) has been reported to be important for stem cell homing and recruitment to injured sites. The aim of this study was to evaluate whether fibroblast growth factor 2 (FGF-2) affects the expression of SDF-1α in PDL cells derived from human permanent teeth in vitro. Using real-time PCR, the expression of SDF-1α mRNA in PDL cells was inhibited by treatment with 10 ng/ml FGF-2. When PDL cells were treated with SU5402 (an inhibitor of FGF receptor 1) in combination with FGF-2, the FGF-2-reduced expression of SDF-1α was inhibited. In the presence of the JNK inhibitor SP600125, SDF-1α mRNA in PDL cells was not suppressed by the FGF-2 treatment. Western blot analysis also showed that SDF-1α production was suppressed by treatment with FGF-2, but it recovered with treatment by FGF-2 + SU5402. These findings suggest that SDF-1α from PDL cells plays an important role in the regeneration and homeostasis of periodontal tissues via the recruitment of stem cells. (キーワード) Cells, Cultured / Chemokine CXCL12 / Fibroblast Growth Factor 2 / Humans / Periodontal Ligament / Pyrroles / RNA, Messenger / Real-Time Polymerase Chain Reaction / Receptor, Fibroblast Growth Factor, Type 1 / Regeneration / Stem Cells / Tooth (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2011.869 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22200847 ● Search Scopus @ Elsevier (PMID): 22200847 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2011.869 (DOI: 10.3892/ijmm.2011.869, PubMed: 22200847)
26.	Mayumi Nomura, Yoshitaka Yoshimura, Takashi Kikuiri, Tomokazu Hasegawa, Yumi Taniguchi, Yoshiaki Deyama, Ken-ichi Koshiro, Hidehiko Sano, Kuniaki Suzuki and Nobuo Inoue : Platinum nanoparticles suppress osteoclastogenesis through scavenging of ROS productions in RAW264.7 cells., Journal of Pharmacological Sciences, Vol.117, No.4, 243-252, 2011. (要約) Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOX-family oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases. (キーワード) Animals / Cell Differentiation / Cell Line / Dose-Response Relationship, Drug / Free Radical Scavengers / Gene Expression Regulation / Macrophages / Mice / Nanoparticles / Osteoclasts / Platinum / RANK Ligand / RNA, Messenger / Reactive Oxygen Species (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.11099FP (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22083043 ● Search Scopus @ Elsevier (PMID): 22083043 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.11099FP (DOI: 10.1254/jphs.11099FP, PubMed: 22083043)
27.	Takashi Kikuiri, Yoshitaka Yoshimura, Futoshi Tabata, Tomokazu Hasegawa, Jun Nishihira and Tetsuo Shirakawa : Stage-dependent suppression of the formation of dentin-resorbing multinuclear cells with migration inhibitory factor in vitro., Experimental and Therapeutic Medicine, Vol.3, No.1, 37-43, 2011. (要約) The macrophage migration inhibitory factor (MIF) is a crucial mediator of immune responses and is known to play a pivotal role in cell proliferation and differentiation. In this study, we assessed whether MIF exerts regulatory effects on osteoclast formation in bone marrow cells and, if so, by what mechanism. Bone marrow cells were either co-cultured with MC3T3-E1 cells or cultured with macrophage-colony stimulating factor (M-CSF) and the soluble form of the receptor activator of the nuclear factor-B ligand (RANKL). Under the influence of MIF, the formation of osteoclastic multinuclear cells was examined. The number of multinuclear TRAP-positive cells formed in the co-culture was significantly reduced when MIF (0.1 g/ml) was exogenously applied during the third and fourth days of the 6-day cultivation period. MIF affected neither the number of mononuclear TRAP-positive cells induced with M-CSF and RANKL, nor the expression of RANKL and osteoprotegerin in MC3T3-E1 cells. TRAP-positive cells cultured on dentin slices with MIF showed lower dentin-resorbing activity than those cultured without MIF. These results suggest that MIF has no regulatory roles in the differentiation of bone marrow cells to mononuclear TRAP-positive cells, but has inhibitory effects on the formation of mature osteoclasts by preventing cell fusion, which may eventually interfere with the osteoclast-mediated dentin resorption. (出版サイトへのリンク) ● Publication site (DOI): 10.3892/etm.2011.362 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22969841 ● Search Scopus @ Elsevier (PMID): 22969841 ● Search Scopus @ Elsevier (DOI): 10.3892/etm.2011.362 (DOI: 10.3892/etm.2011.362, PubMed: 22969841)
28.	Noriko Takahashi, Naoyuki Chosa, Tomokazu Hasegawa, Soko Nishihira, Naoto Okubo, Mamoru Takahashi, Yoshiki Sugiyama, Mitsuro Tanaka and Akira Ishisaki : Dental pulp cells derived from permanent teeth express higher levels of R-cadherin than do deciduous teeth: implications of the correlation between R-cadherin expression and restriction of multipotency in mesenchymal stem cells., Archives of Oral Biology, Vol.57, No.1, 44-51, 2011. (要約) The aim of this study was to characterize the expression status of cadherins in dental pulp-derived mesenchymal progenitor/stem cells from deciduous and permanent teeth, and to determine how cadherins affect the multipotency of the progenitor/stem cells. We evaluated and compared the expression status of cadherins in dental pulp-derived cells from deciduous teeth and in cells from permanent teeth by using an array of primers for amplification of RNA encoding human cell adhesion molecules and a real time PCR system. In order to elucidate how cadherins (which are differentially expressed in deciduous and permanent teeth) affect the multipotency of the dental pulp-derived progenitor/stem cells, the ability of the dental pulp cells to differentiate into adipocytes and osteoblasts was evaluated. R-cadherin was found to be vigorously expressed in the dental pulp cells derived from permanent teeth but not in the dental pulp cells derived from deciduous teeth. N-cadherin was found to be expressed essentially equally in both types of cells. The ability of the dental pulp cells of deciduous teeth to differentiate into adipocytes and osteoblasts was found to be much higher than that of cells obtained from permanent teeth. R-cadherin may be a key molecule for providing control over the multipotency of the dental pulp-derived mesenchymal stem cells. (キーワード) Cadherins / Cell Adhesion Molecules / Cell Culture Techniques / Cell Differentiation / Child / Dental Pulp / Dentition, Permanent / Flow Cytometry / Gene Expression Profiling / Humans / Mesenchymal Stromal Cells / Microscopy, Confocal / RNA / Real-Time Polymerase Chain Reaction / Tooth, Deciduous (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.archoralbio.2011.07.013 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21851926 ● Search Scopus @ Elsevier (PMID): 21851926 ● Search Scopus @ Elsevier (DOI): 10.1016/j.archoralbio.2011.07.013 (DOI: 10.1016/j.archoralbio.2011.07.013, PubMed: 21851926)
29.	Kenjiro Shibata, Yoshitaka Yoshimura, Takashi Kikuiri, Tomokazu Hasegawa, Yumi Taniguchi, Yoshiaki Deyama, Kuniaki Suzuki and Junichiro Iida : Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cells., International Journal of Molecular Medicine, Vol.28, No.1, 73-79, 2011. (要約) The effects of mechanical stress release on osteoclastogenesis may be as important as those of mechanical stress application. However, the direct effects of mechanical stress on the behavior of osteoclasts has not been thoroughly investigated and there is limited information on the results of the release from mechanical stress. In this study, the effects of mechanical stress application and its release on osteoclast differentiation were examined. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts derived from RAW264.7 cells were measured and the expression of osteoclast differentiation genes, which was altered in response to the release from mechanical stress according to the Flexercell tension system was evaluated by real-time PCR. Osteoclast differentiation and fusion were suppressed by mechanical stress application and were rapidly induced after mechanical stress release. The mRNA expression of the osteoclast specific genes, TRAP, matrix metalloproteinase-9 (MMP-9), cathepsin-K (cath-k), calcitonin receptor (CTR), ATPase H+ transporting vacuolar proton pump member I (ATP6i), chloride channel-7 (ClC7) and dendritic cell-specific transmembrane protein (DC-STAMP) was decreased with mechanical stress application, and increased up to 48 h after the release from it. These alterations in gene mRNA expression were associated with the number of osteoclasts and large osteoclasts. Inducible nitric oxide synthetase (iNOS) mRNA was increased with mechanical stress and decreased after its release. Nitric oxide (NO) production was increased with mechanical stress. Nuclear factor of activated T cells cytoplasmic (NFATc) family mRNAs were not altered with mechanical stress, but were up-regulated up to 48 h after the release from it. These findings indicate that the suppression of osteoclast differentiation and fusion induced by mechanical stress is the result of NO increase via iNOS, and that the promotion of osteoclast differentiation and fusion after the release from mechanical stress is related to the NFATc family genes, whose expression remained constant during mechanical stress but was up-regulated after the release from mechanical stress. (キーワード) Acid Phosphatase / Adaptor Proteins, Signal Transducing / Animals / Cathepsin K / Cell Differentiation / Cell Line / Chloride Channels / Gene Expression / Isoenzymes / Matrix Metalloproteinase 9 / Membrane Proteins / Mice / NG-Nitroarginine Methyl Ester / Nitric Oxide / Nitric Oxide Synthase Type II / Osteoclasts / Pressure / Receptors, Calcitonin / Stress, Mechanical / Vacuolar Proton-Translocating ATPases (出版サイトへのリンク) ● Publication site (DOI): 10.3892/ijmm.2011.675 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21491081 ● Search Scopus @ Elsevier (PMID): 21491081 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2011.675 (DOI: 10.3892/ijmm.2011.675, PubMed: 21491081)

学術論文(紀要・その他):

1.	Takeyoshi Asakawa, Naoyuki Chosa, Tomokazu Hasegawa, Asami Asakawa, Akira Isisaki and Mituro Tanaka : Regulation of SDF-1 expression in periodontal ligament cells derived from human permanent teeth, Interface oral health science 2011, 107-109, 2012. (出版サイトへのリンク) ● Publication site (DOI): 10.1007/978-4-431-54070-0_22 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84957037957 (DOI: 10.1007/978-4-431-54070-0_22, Elsevier: Scopus)
2.	Tomokazu Hasegawa, Naoyuki Chosa, Takeyoshi Asakawa, Yoshitaka Yoshimura, Akira Ishisaki and Mitsuro Tanaka : Eatablishment of periodontal ligament cell line derived from human deciduous teeth, Interface oral health science 2011, 114-116, 2012.

総説・解説:

1.	Kimiko Ueda Yamaguchi, Keita Kawarabayashi, Aya Miyazaki, Rika Kurogohshi, Kokoro Iwata, Asuna Sugimoto, Yuki Akazawa, Tomokazu Hasegawa and Tsutomu Iwamoto : Prevention of Sports-related Dental Injuries in Children, Journal of Oral Health and Biosciences, Vol.31, No.1, 68-72, Jul. 2018. (要約) A sports-related dental injury is defined as injuries to the oral and maxillofacial regions associated with sports activities, and involves tooth fracture and luxation, facial bone and temporomandibular fractures, and soft tissue injury. Participants in sports activities are always at risk for traumatic injury, with the oral and maxillofacial region often affected. Dental injuries also have a high rate of occurrence among sports-related injuries received during school physical education classes and club activities. Unfortunately, nearly all such dental injuries are irreversible, and the loss of teeth or their supporting tissues has a significant impact on the quality of life of affected individuals. Thus, for prevention of sports-related dental injuries, it is important for dental professionals to disseminate correct knowledge regarding oral health, as well as provide information to reduce and treat risk factors such as dental caries, periodontal disease, and occlusal problems. In particular, use of mouthguard is one of the most effective ways to prevent sports-related dental injuries that occur in sports and physical activity participants. Recently, along with increased health consciousness, the number of individuals who participate in sports and fitness activities is also increasing. Outside of the bounds of conventional dental clinical treatment, dentists are encouraged to actively be involved in local and regional organizations related to sports, recreation, and physical activity opportunities, in order to contribute to promotion of safety and health, including injury prevention. In this review, we discuss various findings to prevention of sports-related dental injuries in children. (キーワード) Sports injury / Mouthguard / Children (徳島大学機関リポジトリ) ● Metadata: 111941 (出版サイトへのリンク) ● Publication site (DOI): 10.20738/johb.31.1_68 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390845712973017344 ● Search Scopus @ Elsevier (DOI): 10.20738/johb.31.1_68 (徳島大学機関リポジトリ: 111941, DOI: 10.20738/johb.31.1_68, CiNii: 1390845712973017344)
2.	Tsutomu Iwamoto, Asuna Sugimoto, Takamasa Kitamura, Yuki Akazawa and Tomokazu Hasegawa : The role of extracellular ATP-mediated purinergic signaling in bone, cartilage, and tooth tissue, Journal of Oral Biosciences, Vol.56, No.4, 131-135, Jul. 2014. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.job.2014.07.003 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84927910794 (DOI: 10.1016/j.job.2014.07.003, Elsevier: Scopus)
3.	長谷川智一 : 乳歯歯根膜細胞による再生医学研究の可能性の検討, 小児歯科学雑誌, Vol.50, No.1, 7-14, 2012年1月.

国際会議:

1.	Takeyoshi Asakawa, Yoichi Miyamoto, Kentaro Yoshimura, Kiyoto Sasa, Yoko Manome, Ryutaro Kamijo, Tomokazu Hasegawa, Naoyuki Chosa, Akira Ishizaki, Masumi Ookawa, Tomomi Sugiyama, Masayasu Shige and Yukie Shimada : Establish of expression on differentiation periodontal ligament cells derived from human teeth-Cooparative analysis that SDF-1 regulation of expression on periodontal ligament cells derived from Down syndrome teeth, 116, 2017.
2.	Kimiko Ueda Yamaguchi, Asuna Sugimoto, Yuki Akazawa, Tomokazu Hasegawa and Tsutomu Iwamoto : Multi-ion solution promotes cell migration through ERK signaling pathway and CXCR4 expression in human gingival of fibroblasts, 10th Biennial Conferrence of the Pediatric Dentistry Association of Asia, Vol.54, No.2, 346, Tokyo, May 2016.
3.	Takeyoshi Asakawa, Yoichi Miyamoto, Kentaro Yoshimura, Sasa Kiyoto, Tomokazu Hasegawa, Naoyuki Chosa, Akira Ishizaki, Miki Kadena, Yoko Manome, Miku Kuritani, Ryutaro Kamijo and Takahiro Funatsu : Establishing and SDF-1 regulation of expression on periodontal ligament cells derived from human teeth, The Japanese Journal of Pediatric Dentistry, Vol.53, No.2, 354, May 2016. (キーワード) SDF-1 / periodontal ligament / 人間 (human) / permanent teeth
4.	Takeyoshi Asakawa, Naoyuki Chosa, Tomokazu Hasegawa, Asami Asakawa, Akira Ishisaki and Mitsuro Tanaka : Regulation of SDF-1 expression in periodontal ligament cells derived from human permanent teeth., Interface oral health science 2011, 107-109, 2012. (キーワード) fibroblast growth factor-2 / periodontal ligament cells / permanent tooth / stromal cell-derived factor 1
5.	Tomokazu Hasegawa, Naoyuki Chosa, Takeyoshi Asakawa, Yoshimura Yoshitaka, Akira Ishisaki and Mitsuro Tanaka : Eatablishment of periodontal ligament cell line derived from human deciduous teeth., Interface oral health science 2011, 114-116, 2012. (キーワード) deciduous tooth / hTERT / immortalize / priodontal ligament cells

国内講演発表:

1.	上田(山口) 公子, 赤澤友基, 河原林啓太, 宮嵜彩, 北村尚正, 長谷川智一, 中川弘, 岩﨑智憲 : 当院小児摂食嚥下外来における初診時調査, 小児歯科学雑誌, Vol.61, 53-54, 2023年2月.
2.	黒厚子璃佳, 長谷川智一, 岩﨑智憲, 岩本勉 : 両側性に生じた下顎第一大臼歯生歯困難の1例, 日本小児歯科学会, Vol.60, 207, 2022年5月.
3.	岩﨑智憲, 前尾慶, 幸平若菜, 北村尚正, 河原林啓太, 宮嵜彩, 赤澤友基, 上田(山口) 公子, 中川弘, 長谷川智一 : 小児閉塞性睡眠時無呼吸への対応と展望, 徳島県小児保健協会総会並びに第62回講演会, 3, 2021年9月.
4.	黒厚子璃佳, 長谷川智一, 赤澤友基, 岩本勉 : 歯髄細胞におけるFGF2によるJNK経路を介したCCL11の発現抑制, 小児歯科学雑誌, Vol.59, 117, 2021年6月.
5.	宮嵜彩, 長谷川智一, 岩本勉 : 乳歯の早期萌出をみる ADAM17 欠損症の1例, 小児歯科学雑誌, Vol.58, 20, 2020年6月.
6.	熊澤里莉, 守谷有紀, 長谷川智一, 赤澤友基, 岩本勉 : 歯根膜細胞における低酸素環境下でのエピジェネティクス制御の解析, 徳島県歯科医学大会, 36, 2020年2月.
7.	赤澤友基, 岩田こころ, 黒厚子璃佳, 河原林啓太, 宮嵜彩, 藤島史帆, 森浩喜, 杉本明日菜, 北村尚正, 上田(山口) 公子, 中川弘, 長谷川智一, 岩本勉 : 本院小児歯科の初診患者の動向と主訴の変遷について, 徳島県歯科医学大会, 29, 2020年2月.
8.	浅川剛吉, 久木野真純, 長谷川智一, 浅川麻美, 吉村健太郎, 笹清人, 松島瞳, 新田雅一, 永田夏琳, 若月宏之, 杉山智美, 島田幸恵, 上條竜太郎, 船津多敬弘 : ダウン症候群永久歯歯根膜由来細胞のマイクロアレイ比較解析, 小児歯科学雑誌, Vol.58, No.2, 237, 2019年.
9.	杉本明日菜, 宮嵜彩, 河原林啓太, 岩田こころ, 黒厚子璃佳, 赤澤友基, 長谷川智一, 上田(山口) 公子, 北村尚正, 中川弘, 岩本勉 : 象牙芽細胞におけるピエゾ型イオンチャネル1(PIEZO1)の発現とその役割, 第37回日本小児歯科学会中四国地方会大会, 2018年11月.
10.	黒厚子璃佳, 杉本明日菜, 岩田こころ, 宮嵜彩, 河原林啓太, 藤島史帆, 赤澤友基, 北村尚正, 上田(山口) 公子, 尼寺理恵, 長谷川智一, 中川弘, 岩本勉 : 当科における5年間の障害児の初診時実態調査, 第37回日本小児歯科学会中四国地方会大会, 2018年11月.
11.	岩田こころ, 杉本明日菜, 黒厚子璃佳, 河原林啓太, 宮嵜彩, 藤島史帆, 北村尚正, 赤澤友基, 尼寺理恵, 上田(山口) 公子, 中川弘, 長谷川智一, 岩本勉 : 当科における初診患者の実態調査~平成における30年間の変遷~, 第37回日本小児歯科学会中四国地方会大会, 2018年11月.
12.	赤澤友基, 長谷川智一, 岩本勉 : 外傷により両側顎関節完全脱臼を呈した5歳男児の1例, 第37回日本小児歯科学会中四国地方会大会, 2018年11月.
13.	黒厚子璃佳, 長谷川智一, 赤澤友基, 杉本明日菜, 河原林啓太, 上田(山口) 公子, 岩本勉 : 乳歯歯髄細胞におけるExotaxin-1の発現調節機構の解析, 小児歯科学雑誌, Vol.56, No.2, 215, 2018年5月.
14.	浅川剛吉, 大川真澄, 永田夏琳, 長谷川智一, 宮本洋一, 吉村健太, 笹清人, 馬目瑤子, 杉山智美, 上條竜太郎, 島田幸恵 : Down症候群乳歯歯根膜由来細胞のDYRK1A発現解析, 小児歯科学雑誌, Vol.56, No.2, 211, 2018年5月.
15.	黒厚子璃佳, 赤澤友基, 長谷川智一, 杉本明日菜, 上田(山口) 公子, 岩本勉 : 乳歯歯髄細胞におけるケモカインCCL11の発現解析, 小児歯科学雑誌, Vol.56, No.1, 154, 2017年11月.
16.	宮嵜彩, 杉本明日菜, 井上秀人, 北村尚正, 上田(山口) 公子, 河原林啓太, 赤澤友基, 長谷川智一, 岩本勉 : 当科における10年間の口唇口蓋裂児の実態調査, 第55回日本小児歯科学会大会, Vol.55, No.2, 183, 2017年5月.
17.	林光一, 村澤瑛里子, 長谷川智一, 岩本勉 : ヒト乳歯歯髄細胞によるSDF-1αの発現はTGF-βを介してFGF-2により負に制御されている, Journal of Oral Health and Biosciences, 2017年3月.
18.	杉本明日菜, 赤澤友基, 長谷川智一, 宮嵜彩, 河原林啓太, 岩本勉 : PIEZO1は歯髄細胞の分化運命決定に関与し，象牙芽細胞への分化を促進させる, 小児歯科学雑誌, Vol.55, No.2, 290, 2017年.
19.	木舩崇, 伊藤寿典, 石山未紗, 武井浩樹, 長谷川智一, 白川哲夫 : 低酸素暴露が株化歯根膜細胞の血管新生因子産生に及ぼす影響, 小児歯科学雑誌, Vol.55, No.2, 287, 2017年.
20.	宮嵜彩, 杉本明日菜, 井上秀人, 北村尚正, 上田公子, 河原林啓太, 赤澤友基, 長谷川智一, 岩本勉 : 当科における10年間の口唇口蓋裂児の実態調査, 小児歯科学雑誌, Vol.55, No.2, 183, 2017年.
21.	赤澤友基, 長谷川智一, 帖佐直幸, 吉村善隆, 浅川剛吉, 杉本明日菜, 河原林啓太, 宮嵜彩, 石崎明, 岩本勉 : ヒト乳歯歯髄細胞のSDF-1発現調節機構におけるALK5の関与について, 小児歯科学雑誌, Vol.55, No.2, 291, 2017年.
22.	赤澤友基, 上田(山口) 公子, 長谷川智一, 岩本勉 : 低位下顎左側第二乳臼歯の再萌出を認めた1例, 小児歯科学雑誌, Vol.55, No.1, 141-142, 2016年11月.
23.	尼寺理恵, 上田(山口) 公子, 赤澤友基, 北村尚正, 長谷川智一, 杉本明日菜, 岩本勉 : 歯の萌出時期に低濃度フッ素化合物を使用した小児の齲蝕罹患状況, 小児歯科学雑誌, Vol.54, No.1, 144, 2015年10月.
24.	上田(山口) 公子, 赤澤友基, 北村尚正, 杉本明日菜, 長谷川智一, 中川弘, 岩本勉 : ヒト歯肉線維芽細胞におけるS-PRGフィラー抽出液による細胞遊走の促進, 小児歯科学雑誌, Vol.54, No.1, 145, 2015年10月.
25.	上田(山口) 公子, 益富由佳子, 尼寺理恵, 北村尚正, 山本愛美, 赤澤友基, 杉本明日菜, 白石真紀, 中川弘, 長谷川智一, 郡由紀子, 岩本勉 : 当科における小児の乳歯と永久歯の外傷の実態調査, 小児歯科学雑誌, Vol.53, No.2, 272, 2015年5月.
26.	浅川剛吉, 宮本洋一, 吉村健太郎, 長谷川智一, 帖佐直幸, 石崎明, 山下一恵, 嘉手納未季, 馬目瑤子, 栗谷未来, 上條竜太郎, 船津敬弘 : ヒトDown症候群歯根膜由来細胞におけるSDF-1α発現解析, 小児歯科学雑誌, Vol.53, No.2, 265, 2015年.
27.	赤澤友基, 長谷川智一, 岩本勉 : 象牙質修復に関わる間葉系幹細胞の乳歯歯髄細胞由来SDF-1αによる制御, 小児歯科学雑誌, Vol.53, No.2, 221, 2015年.
28.	長谷川智一, 赤澤友基, 吉村善隆, 帖佐直幸, 浅川剛吉, 杉本明日菜, 北村尚正, 上田(山口) 公子, 中川弘, 白石真紀, 石崎明, 岩本勉 : 乳歯歯根膜由来細胞のSDF-1αを介した歯周組織恒常性に関わる細胞間相互作用, 小児歯科学雑誌, Vol.53, No.2, 222, 2015年.
29.	真杉幸江, 赤澤友基, 長谷川智一, 岩本勉 : 先天性気管狭窄症に対する口腔内衛生管理の1例, 小児歯科学雑誌, Vol.53, No.1, 168, 2015年.
30.	浅川剛吉, 宮本洋一, 吉村健太郎, 長谷川智一, 山下一恵, 嘉手納美季, 馬目瑤子, 栗谷未来, 上条竜太郎, 船津敬弘 : ヒトDown症乳歯歯根膜細胞のSDF-1発現調節の解析, 障害者歯科, Vol.35, No.3, 278, 2014年.
31.	吉村善隆, 早川貴子, 長谷川智一, 出山義昭, 鈴木邦明, 飯田順一郎 : 至適圧縮力は破骨細胞分化を促進する, 歯基礎誌抄録, 189, 2014年.
32.	北村尚正, 中川弘, 杉本明日菜, 赤澤友基, 長谷川智一, 岩本勉 : 含歯性嚢胞の間葉系結合組織層が骨吸収に与える影響, 歯基礎誌抄録, 141, 2014年.
33.	中川弘, 山本愛美, 赤澤友基, 北村尚正, 長谷川智一, 岩本勉 : p-HPPHを分子標的としたフェニトインによる歯肉増殖症に対する新規治療薬の開発, 障害者歯科, Vol.35, No.3, 478, 2014年.
34.	北村尚正, 郡由紀子, 赤澤友基, 長谷川智一, 岩本勉 : 鼻腔底に近接した上顎正中埋伏過剰歯由来の含歯性嚢胞の1例, 小児歯科学雑誌, Vol.52, No.2, 306, 2014年.
35.	赤澤友基, 長谷川智一, 久保-藤原百合, 北村尚正, 上田(山口) 公子, 中川弘, 岩本勉 : 当科にて長期的口腔内管理を行った伊藤白斑の1例, 小児歯科学雑誌, Vol.52, No.2, 354, 2014年.
36.	長谷川智一, 赤澤友基, 北村尚正, 上田(山口) 公子, 中川弘, 岩本勉 : 幼児期の小児の口蓋に発生した血管腫の1例, 小児歯科学雑誌, Vol.52, No.2, 355, 2014年.
37.	長谷川智一, 赤澤友基, 中川弘, 上田公子, 岩本勉 : 乳歯歯髄細胞による細胞走化性因子の調節機構, 小児歯科学雑誌, Vol.52, No.1, 125-126, 2014年.
38.	長谷川智一, 久保-藤原百合, 赤澤友基, 北村尚正, 上田(山口) 公子, 岩本勉 : 当科において口腔内管理を行ってきた滑脳症を伴った伊藤白斑の1症例, 小児歯誌, Vol.52, No.1, 184-185, 2014年.
39.	上田(山口) 公子, 山本愛美, 郡由紀子, 中川弘, 長谷川智一, 岩本勉 : 上顎中切歯の萌出遅延を起こした集合性歯牙腫の1症例, 第32回日本小児歯科学会中四国地方会大会, Vol.52, No.1, 180-181, 2013年11月.
40.	上田(山口) 公子, 郡由紀子, 山本愛美, 赤澤友基, 北村尚正, 中川弘, 長谷川智一, 岩本勉 : 過剰歯摘出によって歯の位置異常が改善した症例についての検討, 第31回日本小児歯科学会北日本地方会大会, Vol.52, No.1, 122-123, 2013年10月.
41.	中川弘, 山本愛美, 郡由紀子, 上田(山口) 公子, 赤澤友基, 北村尚正, 長谷川智一, 岩本勉 : 歯科治療恐怖症患者に応用した心理検査結果の経時的変化について, 障害者歯科, Vol.34, No.3, 375, 2013年10月.
42.	長谷川智一, 赤澤友基, 帖佐直幸, 吉村善隆, 浅川剛吉, 石崎明, 岩本勉 : ヒト乳歯歯髄細胞におけるSDF-1の発現調節機構, 第55回歯科基礎医学会学術大会, 2013年9月.
43.	赤澤友基, 長谷川智一, 帖佐直幸, 吉村善隆, 浅川剛吉, 石崎明, 岩本勉 : ヒト乳歯歯髄細胞由来の不死化細胞は骨および脂肪細胞への分化能を持つ, 第55回歯科基礎医学会学術大会, 2013年9月.
44.	中川弘, 山本愛美, 郡由紀子, 上田(山口) 公子, 赤澤友基, 北村尚正, 長谷川智一, 岩本勉 : 歯科治療恐怖症患者に応用した心理検査結果の経時的変化について, 障害者歯科, Vol.34, No.3, 375, 2013年9月.
45.	赤澤友基, 帖佐直行, 吉村善隆, 北村尚正, 藤原百合, 浅川剛吉, 石崎明, 長谷川智一 : ヒト乳歯歯髄細胞の細胞株樹立, 小児歯科学雑誌, Vol.51, No.2, 303, 2013年4月. (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1572261551063864576 (CiNii: 1572261551063864576)
46.	上田公子, 山本愛美, 郡由紀子, 中川弘, 長谷川智一, 岩本勉 : 上顎中切歯の萌出遅延を起こした集合性歯牙腫の1症例, 小児歯科学雑誌, Vol.52, No.1, 180-181, 2013年.
47.	吉村善隆, 亀山純香, 菊入崇, 長谷川智一, 出山義昭, 鈴木邦明, 飯田順一郎 : 機械的刺激はDC-STAMPの発現抑制によりRAW264.7細胞の破骨細胞分化誘導を抑制する, 歯基礎誌抄録, 205, 2013年.
48.	横田潤, 帖佐直幸, 高橋典子, 衣斐美歩, 客本斉子, 加茂政晴, 長谷川智一, 近藤尚知, 石崎明 : 複数サイトカインによる同時刺激は間葉系幹細胞の骨分化誘導能を促進する, 歯基礎誌抄録, 189, 2013年.
49.	青松恵美子, 帖佐直幸, 衣斐美歩, 客本斉子, 加茂政晴, 長谷川智一, 佐藤和郎, 三浦廣行, 石崎明 : 間葉系幹細胞が分泌するSCRG1は骨分化を抑制する, 歯基礎誌抄録, 188, 2013年.
50.	赤澤友基, 長谷川智一, 帖佐直幸, 吉村善隆, 浅川剛吉, 石崎明, 岩本勉 : ヒト乳歯歯髄組織由来の不死化細胞は骨および脂肪細胞への分化能を持つ, 歯科基礎誌抄録, 188, 2013年.
51.	長谷川智一, 赤澤友基, 帖佐直幸, 吉村善隆, 浅川剛吉, 石崎明, 岩本勉 : ヒト乳歯歯髄細胞におけるSDF-1の発現調節機構, 歯科基礎誌抄録, 192, 2013年.
52.	中川弘, 山本愛美, 郡由紀子, 赤澤友基, 北村尚正, 長谷川智一, 岩本勉 : 歯科治療恐怖症患者に応用した心理検査結果の経時的変化について, 障害者歯科, Vol.34, No.3, 375, 2013年.
53.	長谷川智一, 赤澤友基, 帖佐直行, 吉村善隆, 北村尚正, 藤原百合, 浅川剛吉, 石崎明 : ヒト乳歯歯髄細胞株におけるFGF-2によるSDF-1α発現調節機構の解析, 小児歯誌, Vol.51, No.2, 164, 2013年.
54.	赤澤友基, 郡由紀子, 尼寺理恵, 上田(山口) 公子, 山本愛美, 長谷川智一, 北村尚正, 藤原百合 : 集合性歯牙腫が上顎乳前歯の萌出障害を起こした1症例, 第31回日本小児歯科学会中四国地方会大会及び総会, Vol.51, No.1, 115, 2012年11月.
55.	長谷川智一, 帖佐直幸, 藤原百合, 北村尚正, 浅川剛吉, 赤澤友基, 吉村善隆, 石崎明, 三留雅人 : 乳歯歯根膜はSDF-1αにより間葉系幹細胞の遊走をコントロールし，歯周組織の再生・恒常性に関与している, 小児歯誌, Vol.50, No.2, 240, 2012年5月.
56.	藤原百合, 長谷川智一, 赤澤友基, 北村尚正, 三留雅人 : 色素失調症により多数歯欠損がみられた症例, 小児歯誌, Vol.50, No.1, 120, 2012年.
57.	長谷川智一 : 乳歯歯根膜細胞による再生医学研究の可能性の検討, 小児歯科学雑誌, Vol.49, No.41, 51, 2011年1月.
58.	吉田茉莉子, 大久保直登, 帖佐直幸, 長谷川智一, 高橋典子, 衣斐美歩, 客本斉子, 加茂政晴, 石崎明 : 歯周靭帯由来細胞の血管構成細胞分化におけるTGF-βの関与について, 歯基礎誌, Vol.53, 139, 2011年.
59.	高橋美香子, 大久保直登, 帖佐直幸, 高橋典子, 長谷川智一, 客本斉子, 加茂政晴, 水城春美, 石崎明 : 歯周靭帯由来線維芽細胞の増殖と平滑筋分化はFGFで誘導されるERKシグナルにより制御される, 歯基礎誌, Vol.35, 182, 2011年.
60.	浅川剛吉, 帖佐直幸, 長谷川智一, 浅川麻美, 石崎明, 田中光郎 : ヒト永久歯歯根膜細胞におけるSDF-1発現調節の解析, 小児歯科学雑誌, Vol.49, No.4, 367, 2011年.
61.	長谷川智一, 帖佐直幸, 浅川剛吉, 浅川麻美, 吉村善隆, 石崎明, 田中光郎 : ヒト乳歯歯根膜細胞におけるFGF-2およびTGF-β1によるSDF-1発現への影響, 小児歯誌, Vol.49, No.4, 368, 2011年.
62.	福本敏, 吉崎恵悟, 山田亜矢, 山本晋也, 岩本勉, 湯浅健司, 長谷川智一, 福本恵美子, 野中和明 : エナメル芽細胞の分化機構とその制御, 第30回分子生物学会，第80回生化学会合同年会ワークショップ「歯の発生・再生の分子メカニズム」, 2007年12月.
63.	新垣真紀子, 山田亜矢, 湯浅健司, 野中和明, 長谷川智一, 岡暁子, 岩本勉, 福本敏 : 下顎第二乳臼歯の完全埋伏や萠出異常を認めた症例, 第25回日本小児歯科学会九州地方会大会, 2007年11月.
64.	福本敏, 自見英治郎, 福島秀文, 岩本勉, 山田亜矢, 湯浅健司, 長谷川智一, 福本恵美子, 山口登, 野中和明 : 歯冠幅径を規定する分子シグナルの同定, 第45回日本小児歯科学会大会, 2007年7月.

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

間葉系幹細胞の骨芽細胞分化におけるメカノセンサー、メカノトランスダクションの解明 (研究課題/領域番号: 23K09436 )
Down症候群歯根膜由来細胞による骨髄間葉系幹細胞遊走因子発現解析 (研究課題/領域番号: 20K10235 )
乳歯歯髄組織におけるCCL11の機能解析および新たな歯髄保護再生療法の開発 (研究課題/領域番号: 20K10205 )
細胞外圧による間葉系幹細胞の分化運命制御機構の解明 (研究課題/領域番号: 17H04414 )
歯根膜組織の再生・恒常性維持マシナリーに関与する新機能の探索および応用法の開発 (研究課題/領域番号: 16K11804 )
骨髄間質細胞由来因子による歯周組織再生療法の開発-Down症歯根膜細胞の解析ー (研究課題/領域番号: 16K11812 )
基質小胞分泌メカニズムの解明と石灰化への応用 (研究課題/領域番号: 15K11368 )
前象牙芽細胞の役割解明と象牙質再生への応用 (研究課題/領域番号: 26293435 )
歯周組織の恒常性維持機構における歯根膜機能の解析および新しい歯周組織再建法の開発 (研究課題/領域番号: 25463182 )
乳歯歯根膜由来細胞株の樹立および歯根膜細胞による新しい歯周組織再生法の開発 (研究課題/領域番号: 22592296 )
性質の異なる破骨細胞に着目した病的・非生理的歯根吸収機構の解明 (研究課題/領域番号: 22592274 )
乳歯歯根吸収に関与する遺伝子の探索およびその制御機構の分子生物学的解析 (研究課題/領域番号: 18592239 )
歯の発生・分化におけるIKK-γによる転写制御ネットワークの解析 (研究課題/領域番号: 17592125 )
母体脳標的遺伝子導入による胎生期・吸啜期の母仔間相互作用の解析 (研究課題/領域番号: 17390555 )
修復材料の溶出成分が小児歯周組織の免疫反応に与える影響の解析 (研究課題/領域番号: 13877349 )
乳歯歯根吸収に関与する遺伝子の同定およびその制御機構の分子生物学的解析 (研究課題/領域番号: 12771265 )
宿主側の歯周病罹患リスクファクターの分子生物学的解析とその治療法の検討-歯周組織の老化に関する研究- (研究課題/領域番号: 12557178 )
ヒト歯根膜細胞における伸展活性化メカニズムの解明 (研究課題/領域番号: 12470455 )
口腔癌顎骨浸潤における破骨細胞と癌細胞の相互作用に関する研究 (研究課題/領域番号: 12470432 )
新しい細菌検査法による乳歯の病的歯根吸収過程の解明と治療法の確立 (研究課題/領域番号: 11470445 )
乳歯歯根吸収に関する遺伝子の同定と吸収制御メカニズムの解明 (研究課題/領域番号: 10771188 )
ヒト歯根細胞の機能調節に関わる分子群の検索 (研究課題/領域番号: 09470464 )
ヒト乳歯・永久歯歯髄細胞株の樹立および新しい細胞毒性試験の開発 (研究課題/領域番号: 08672378 )
研究者番号（50274668）による検索

講師 : 長谷川智一

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科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

講師 : 長谷川 智一

研究活動

専門分野

研究テーマ

著書・論文

著書:

学術論文(審査論文):

学術論文(紀要・その他):

総説・解説:

国際会議:

国内講演発表:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

講師 : 長谷川智一