
講座概要
間葉系幹細胞や口腔組織由来細胞における生命現象について細胞内シグナル伝達系を中心とした分子レベルで解析することで、口腔組織をはじめ全身の各組織再生や各種疾患発症の分子機構の解明を目指した研究を実施している。
教授挨拶

生化学は細胞の分子組成、生体成分の化学反応、生体化学反応の調節を研究する学問です。また、生化学の中で重要な位置を占める分子生物学は遺伝子の構造、機能、調節を明らかにする学問です。
学部学生の生化学理解のため、講義は「一般生化学」「口腔生化学」にわけ、それぞれ1学年と2学年で学習します。特に、口腔生化学では臨床科目の生化学的側面を理解できるよう学びます。加えて、細胞培養技術、生化学的手法、分子生物学的手法を用いて大学院生の研究指導も実施しています。現在、複数の大学院生がスタッフのきめ細やかな指導のもとに研究生活を送っています。研究仲間が多く研究室は明るく活気に満ちています。
講座スタッフ
| 教授 | 石崎 明 | いしさき あきら |
| 准教授 | 帖佐 直幸 | ちょうさ なおゆき |
| 講師 | 横田 聖司 | よこた せいじ |
講座における主たる研究テーマ
- 間葉系細胞の増殖・分化の制御機構の解明
- 口腔組織由来細胞の増殖・分化の制御機構の解明
- 口腔扁平上皮がん細胞の浸潤・転移の分子メカニズムの解明
講座の主な業績
【令和7(2025)年度】
- Abe K, Yokota S, Matsumoto S, Ujiie H, Kikuchi E, Satoh K, Ishisaki A, Chosa N. “Proinflammatory cytokine-induced matrix metalloproteinase-9 expression in temporomandibular joint osteoarthritis is regulated by multiple intracellular mitogen-activated protein kinase pathways”. Journal of Oral Biosciences, 67:100609, 2025.
【令和6(2024)年度】
- Yoshida H, Yokota S, Satoh K, Ishisaki A, Chosa N. “Connective tissue growth factor enhances TGF-β1-induced osteogenic differentiation via activation of p38 MAPK in mesenchymal stem cells”. Journal of Oral Biosciences, 66:68-75, 2024.
- Obara N, Kyakumoto S, Yamaguchi S, Yamada H, Ishisaki A, Kamo M. “Disruption of CADM1-dependent cell-cell adhesion in human oral squamous cell carcinoma cells results in tumor progression, possibly through an increase of MMP-2 and MMP-9 expression”. Journal of Oral Biosciences, 66:151-159, 2024.
【令和5(2023)年度】
- Asanuma K, Yokota S, Chosa N, Kamo M, Ibi M, Mayama H, Irie T, Satoh K, Ishisaki A. “Hydrogen peroxide-induced oxidative stress promotes expression of CXCL15/Lungkine mRNA in a MEK/ERK-dependent manner in fibroblast-like synoviocytes derived from mouse temporomandibular joint”. Journal of Oral Biosciences, 65:97-103, 2023.
- Yokota S, Chosa N, Matsumoto S, Satoh K, Ishisaki A. “Extracellular adenosine 5′-diphosphate promotes MCP-1/CCL2 expression via the P2Y13 purinergic receptor/ERK signaling axis in temporomandibular joint-derived mouse fibroblast-like synoviocyte”. Molecular Biology Reports, 50:1595-1602, 2023.
【令和4(2022)年度】
- Miyamae Y, Ohta M, Sato K, Ishisaki A, Chosa N. “TGF-β1-induced IL-6 expression via MEK pathway in mesenchymeal stem cells enhances NGF-dependent neurite extension in PC12 cells”. Dental Journal of Iwate Medical University, 47:19-33, 2022.
- Ishikawa Y, Hirano T, Yamada H, Ishisaki A, Kamo M. “Sclerostin derived from EMT-promoted human oral squamous cell carcinoma cells induces IL-6-, and IL-17A-mediated M1 to M2 polarization shift in THP-1-derived macrophages”. Dental Journal of Iwate Medical University, 47:34-50, 2022.
- Koizumi R, Kuroshima S, Kaneko H, Sasaki M, Ishisaki A, Sawase T. “Zoledronic acid deteriorates soft and hard tissue healing of murine tooth extraction sockets in a dose-dependent manner”. Calcified Tissue International, 110:104-116, 2022.
【令和3(2021)年度】
- Takeda K, Ishikawa Y, Yamada H, Ishisaki A, Kamo M. “CCL20 derived from PMA-differentiated macrophages abrogates TGF-β1-induced expression of cancer progression suppressor CXCL14 in HSC-4 cells PI3K-, MEK1/2-, and NF-κB-dependent manners”. Dental Journal of Iwate Medical University, 46:19-32, 2021.
【令和2(2020)年度】
- Tamaki S, Kuroshima S, Hayano H, Nakajima K, Kakehashi H, Ishisaki A, Sawase T. “Dynamic polarization shifting from M1 to M2 macrophages in reduced osteonecrosis of the jaw-like lesions by cessation of anti-RANKL antibody in mice”. Bone, 141:115560, 2020.
- Hirano T, Saito D, Yamada H, Ishisaki A, Kamo M. “TGF-β1 induces N-cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation in human oral squamous cell carcinoma cells”. Oncology Letters, 20:474-482, 2020.
- Hirano T, Saito D, Komatsu Y, Yamada H, Ishisaki A, Kamo M. “YAP/TAZ activation, induced by disruption of E-cadherin-mediated cell-to-cell contact, promotes the cadherin switch by facilitating nuclear translocation of Slug in human oral squamous cell carcinoma HSC-4 cells”. Dental Journal of Iwate Medical University, 45:23-34, 2020.
- Matsumoto S, Yokota S, Chosa N, Kyakumoto S, Kimura H, Kamo M, Satoh K, Ishisaki A. “Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular-joint-derived fibroblast-like synoviocytes via mitogen-activated protein kinase kinase/extracellular signal-regulated kinase”. Experimental and Therapeutic Medicine, 20:1967-1974, 2020.
- Matsumoto S, Yokota S, Kyakumoto S, Chosa N, Satoh K. “Adenosine 5′-triphosphate strengthens receptor tyrosine kinase-mediated suppression of fibrogenic activity in fibroblast-like synoviocytes derived from mouse temporomandibular joints possibly through P2Y2, P2Y4, and P2Y13 purinergic receptors”. Dental Journal of Iwate Medical University, 45: 46-57, 2020.
- Hayano H, Kuroshima S, Sasaki M, Tamaki S, Inoue M, Ishisaki A, and Sawase T. “Distinct immunopathology in the early stages between different antiresorptives-related osteonecrosis of the jaw-like lesions in mice”. Bone, 135:115308, 2020.
【平成30(2018)年度】
- Ohta M., Chosa N., Kyakumoto S., Yokota S., Okubo N., Nemoto A., Kamo M., Joh S., Satoh K., Ishisaki A. “IL-1β and TNF-α suppress TGF-β-promoted NGF expression in periodontal ligament-derived fibroblasts through inactivation of TGF-β-induced Smad2/3-, and p38 MAPK-mediated signals”. International Journal of Molecular Medicine, 43:1484-1494, 2018.
- Ibi M., Horie S., Kyakumoto S., Chosa N., Yoshida M., Kamo M., Ohtsuka M., Ishisaki A. “Cell-cell interactions between monocytes/macrophages and synoviocyte-like cells promote inflammatory cell infiltration mediated by augmentation of MCP-1 production in temporomandibular joint”. Bioscience Reports, 38:BSR20171217, 2018.
- Ohta M.*, Nemoto A.*, Chosa N., Kyakumoto S., Yokota S., Kamo M., Shibata S., Joh S., Satoh K., Ishisaki A. “Toll-like receptor 4-mediated signaling activated by lipopolysaccharide suppresses transforming growth factor-beta-induced nerve growth factor expression in periodontal ligament-derived fibroblasts”. Dental Journal of Iwate Medical University, 43:61-73, 2018. *co-first authors.
- Chosa N., Ishisaki A. “Two novel mechanisms for maintenance of stemness in mesenchymal stem cells: SCRG1/BST1 axis and cell-cell adhesion through N-cadherin”. Japanese Dental Science Review, 54:37-44, 2018.
- Nemoto A., Chosa N., Kyakumoto S., Yokota S., Kamo M., Noda M., Ishisaki A. “Water-soluble factors eluated from surface pre-reacted glass-ionomer filler promote osteoblastic differentiation of human mesenchymal stem cells”. Molecular Medicine Reports, 17:3448-3454, 2018.
【平成29(2017)年度】
- Takizawa N.*, Okubo N.*, Kamo M., Chosa N., Mikami T., Suzuki K., Yokota S., Ibi M., Ohtsuka M., Taira M., Yaegashi T., Ishisaki A., Kyakumoto S. “Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture”. Experimental Cell Research, 358:411-420, 2017. *co-first authors.
- Kanno Y., Maruyama C., Matsuda A., Ishisaki A. “uPA-derived peptide, A6 is involved in the suppression of lipopolysaccaride-promoted inflammatory osteoclastogenesis and the resultant bone loss”. Immunity, Inflammation and Disease, 5:289-299, 2017.
- Kanno Y., Ishisaki A., Kuretake H., Maruyama C., Matsuda A., Matsuo O. “Alpha2-antiplasmin modulates bone formation by negatively regulating the osteoblast differentiation and its function”. International Journal of Molecular Medicine, 40:854-858, 2017.
- Inoue M., Yamada J, Aomatsu-Kikuchi E., Satoh K., Kondo H., Ishisaki A., Chosa N. “SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells”. Molecular Medicine Reports, 15:4069-4076, 2017.
- Inoue M., Ohtsu K., Ohtsuka M., Takafuji K., Harada H., Ishisaki A., Kondo H. “Healing mechanism surrounding transplanted bone using transgenic mice expressing red fluorescent protein in vivo”. Journal of Oral Tissue Engineering, 14:74-85, 2017.
- Yokota S., Chosa N., Kyakumoto S., Kimura H., Ibi M., Kamo M., Satoh K., Ishisaki A. “ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint”. International Journal of Molecular Medicine, 39:799-808, 2017.
- Suzuki K.*, Chosa N.*, Sawada S., Takizawa N., Yaegashi T., Ishisaki A. “Enhancement of anti-inflammatory and osteogenic abilities of mesenchymal stem cells via cell-to-cell adhesion to periodontal ligament-derived fibroblasts”. Stem Cells International, 2017:3296498, 2017. *co-first authors.
- Chiba T., Ishisaki A., Kyakumoto S., Shibata T., Yamada H., Kamo M. “Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression”. Oncology Reports, 37:713-720, 2017.
【平成28(2016)年度】
- Bologna-Molina R., Takeda Y., Kuga T., Chosa N., Kitagawa M., Takata T., Ishisaki A., Mikami T. “Expression of Wilms’ tumor 1 (WT1) in ameloblastomas”. Journal of Oral Science, 58:407-413, 2016.
- Kanno Y., Ishisaki A., Miyashita M., and Matsuo O. “The blocking of uPAR suppresses lipopolysaccharide-induced inflammatory osteoclastogenesis and the resultant bone loss through attenuation of integrin β3/Akt pathway”. Immunity, Inflammation and Disease, 4:338-349, 2016.
- Komatsu Y., Ibi M., Chosa N., Kyakumoto S., Kamo M., Shibata T., Sugiyama Y., Ishisaki A. “Zoledronic acid suppresses transforming growth factor-β (TGF-β)-induced fibrogenesis by human gingival fibroblasts possibly through down-regulation of TGF-β type I receptor expression”. International Journal of Molecular Medicine, 38:139-147, 2016.
- Hino M., Kamo M., Saito D., Kyakumoto S., Shibata T., Mizuki H., Ishisaki A. “Transforming growth factor-β1 induces invasion ability of HSC-4 human squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signaling axis”. Journal of Biochemistry, 159:631-640, 2016.
- Igarashi Y.*, Chosa N.*, Sawada S., Kondo H., Yaegashi T., Ishisaki A. “VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes”. International Journal of Molecular Medicine, 37:1005-1013, 2016. *co-first authors.
- Sawada S.*, Chosa N.*, Takizawa N., Yokota J., Igarashi Y., Tomoda K., Kondo H., Yaegashi T., Ishisaki A. “Establishment of mesenchymal stem cell lines derived from the bone marrow of GFP-transgenic mice exhibiting diversity in intracellular TGF-β and BMP signaling”. Molecular Medicine Reports, 13:2023-2031, 2016. *co-first authors.
- Kanno Y., Ishisaki A., Kawashita E., Kuretake H., Ikeda K., Matstuo O. “uPA attenuated LPS-induced inflammatory osteoclastogenesis through the plasmin/PAR-1/Ca2+/CaMKK/AMPK axis”. International Journal of Biological Sciences, 12:63-71, 2016.
【平成27(2015)年度】
- Furukawa S.*, Kuwajima Y.*, Chosa N., Satoh K., Ohtsuka M., Miura H., Kimura M., Inoko H., Ishisaki A., Fujimura A., Miura H. “Establishment of immortalized mesenchymal stem cells derived from the submandibular glands of tdTomato transgenic mice”. Experimental and Therapeutic Medicine, 10:1380-1386, 2015. *co-first authors.
- Akazawa Y., Hasegawa T., Yoshimura Y., Chosa N., Asakawa T., Ueda K., Sugimoto A., Kitamura T., Nakagawa H., Ishisaki A., Iwamoto T. “Recruitment of mesenchymal stem cells by stromal cell-derived factor 1α in pulp cells from deciduous teeth”. International Journal of Molecular Medicine, 36:442-448, 2015.
- Kuramitsu-Fujimoto S., Saito N., Ariyoshi W., Okinaga T., Kamo M., Ishisaki A., Takata T., Yamaguchi K., and Nishihara T. “Novel biological activity of ameloblastin in enamel matrix derivative”. Journal of Applied Oral Science, 23:49-55, 2015.
- Nakajima K., Itoh F., Nakamura M., Kawamura A., Yamazaki T., Kozakai T., Takusari M., Ishisaki A. “Opposing effects of lactoferrin on the proliferation of fibroblasts and epithelial cells from bovine mammary gland”. Journal of Dairy Science, 98:1069-1077, 2015.
【平成26(2014)年度】
- Taira M., Hatakeyama W., Yokota J., Chosa N., Ishisaki A., Takafuji K., Kihara H., Kondo H., Hattori M. “Tracking GFP-labeled transplanted mouse MSC in nude mice using in vivo fluorescence imaging”. Nano Biomedicine, 6:73-77, 2014.
- Tamaoki N., Takahashi K., Aoki H., Iida K., Kawaguchi T., Hatakeyama D., Inden M., Chosa N., Ishisaki A., Kunisada T., Shibata T., Goshima N., Yamanaka S., Tezuka K. “The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells”. Scientific Reports, 4:7283, 2014.
- Asano T., Taoka M., Yamauchi Y., Everroad C.R., Seto Y., Isobe T., Kamo M., Chosa N. “Re-examination of a α-chymotrypsin-solubilized laccase in the pupal cuticle of the silkworm, Bombyx mori: insights into the regulation system for laccase activation during the ecdysis process”. Insect Biochemistry and Molecular Biology, 55:61-69, 2014.
- Aomatsu E., Takahashi N., Sawada S., Okubo N., Hasegawa T., Taira M., Miura H., Ishisaki A., Chosa N. “Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells”. Scientific Reports, 4:3652, 2014.
- Matsui M., Chosa N., Shimoyama Y., Minami K., Kimura S., Kishi M. “Effects of tongue cleaning on bacterial flora in tongue coating and dental plaque: A crossover study”. BMC Oral Health, 14:4, 2014.
- Aomatsu E.*, Chosa N.*, Nishihira S., Sugiyama Y., Miura H., Ishisaki A. “Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFRβ in a ligand-independent manner in mesenchymal stem cells”. International Journal of Molecular Medicine, 33:565-572, 2014. *co-first authors.
- Yokota J., Chosa N., Sawada S., Okubo N., Takahashi N., Hasegawa T., Kondo H., Ishisaki A. “PDGF-induced PI3K-mediated signal enhances TGF-β-induced osteogenic differentiation of human mesenchymal stem cells in the TGF-β-activated MEK-dependent manner”. International Journal of Molecular Medicine, 33:534-542, 2014.
【平成25(2013)年度】
- Kimura H.*, Okubo N.*, Chosa N., Kyakumoto S., Kamo M., Miura H., Ishisaki A. “EGF positively regulates the proliferation and migration, and negatively regulates the myofibroblast differentiation of periodontal ligament-derived endothelial progenitor cells through MEK/ERK- and JNK-dependent signals”. Cellular Physiology and Biochemistry, 32:899-914, 2013. *co-first authors.
- Hatakeyama W., Taira M., Chosa N., Kihara H., Ishisaki A., Kondo H. “Effects of apatite particle size contained in two apatite/collagen composites on osteogenic differentiation profile in osteoblastic cells”. International Journal of Molecular Medicine, 32:1255-1261, 2013.
- Sawada S., Chosa N., Ishisaki A., Naruishi K. “Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6”. Biomedical Research, 43:31-40, 2013.
- Takizawa N., Sawada S., Chosa N., Ishisaki A., Naruishi K. “Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts”. Biomedical Research, 43:1-11, 2013.
- Saito D., Kyakumoto S., Chosa N., Ibi M., Takahashi N., Okubo N., Sawada S., Ishisaki A., Kamo M. “Transforming growth factor-β1 induces epithelial-mesenchymal transition and integrin α3β1-mediated cell migration of HSC-4 human squamous cell carcinoma cells through Slug”. Journal of Biochemistry, 153:303-315, 2013.
- Mikami T., Hada T., Chosa N., Ishisaki A., Mizuki H., Takeda Y. “Expression of WT1 (Wilms’ tumor 1) in oral squamous cell carcinoma”. Journal of Oral Pathology and Medicine, 42:133-139, 2013.
【平成24(2012)年度】
- Yoshida M.*, Okubo N.*, Chosa N., Hasegawa T., Ibi M., Kamo M., Kyakumoto S., Ishisaki A. “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, 8:1062-1074, 2012. *co-first authors.
- Shenton M.R., Berberich T., Kamo M., Yamashita T., Taira H., Terauchi R. “Use of intercellular washing fluid to investigate the secreted proteome of the rice-Magnaporthe interaction”. Journal of Plant Research, 125:311-316, 2012.
- Inoko A., Matsuyama M., Goto H., Ohmuro-Matsuyama Y., Hayashi Y., Enomoto M., Ibi M., Urano T., Yonemura S., Kiyono T., Izawa I., Inagaki M. “Trichoplein and Aurora A block aberrant primary clia assembly in proliferating cells”. Journal of Cell Biology, 197:391-405, 2012.
- Hasegawa T., Chosa N., Asakawa T., Yoshimura Y., Fujihara Y., Kitamura T., Tanaka M., Ishisaki A., Mitome M. “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, 30:35-40, 2012.
- Asakawa T., Chosa N., Yoshimura Y., Asakawa A., Tanaka M., Ishisaki A., Mitome M., Hasegawa T. “Fibroblast growth factor 2 inhibits the expression of stromal cell-derived factor 1α in periodontal ligament cells derived from human permanent teeth in vitro”. International Journal of Molecular Medicine, 29:569-573, 2012.
- Takahashi M., Okubo N., Chosa N., Takahashi N., Ibi M., Kamo M., Mizuki H., Ishisaki A., Kyakumoto S. “Fibroblast growth factor-1-induced ERK1/2 signaling reciprocally regulates proliferation and smooth muscle cell differentiation of ligament-derived endothelial progenitor cell-like cells”. International Journal of Molecular Medicine, 29:357-364, 2012.
- Takahashi N., Chosa N., Hasegawa T., Nishihira S., Okubo N., Takahashi M., Sugiyama Y., Tanaka M., Ishisaki A. “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, 57:44-51, 2012.
【平成23(2011)年度】
- Nakajima K., Kanno Y., Nakamura M., Gao X-D., Kawamura A., Itoh F., Ishisaki, A. “Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway”. Biometals, 24:847-856, 2011.
- Kanno Y., Ishisaki A., Kawashita E., Chosa N., Nakajima K., Nishihara T., Toyoshima K., Okada K., Ueshima S., Matsushita K., Matsuo O., Matsuno H. “Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function”. Journal of Biological Chemistry, 286:8952-8960, 2011.
- Nishihira S., Okubo N., Takahashi N., Ishisaki A., Sugiyama Y., Chosa N. “High-cell density-induced VCAM1 expression inhibits the migratory ability of mesenchymal stem cells”. Cell Biology International, 35:475-481, 2011.
- Ibi M.*, Zou P.*, Inoko A.*, Shiromizu T., Matsuyama M., Hayashi Y., Enomoto M., Mori D., Hirotsune S., Kiyono T., Tsukita S., Goto H., Inagaki M. “Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein”. Journal of Cell Science, 124:857-864, 2011. *co-first authors.
【平成22(2010)年度】
- Hasegawa T., Chosa N., Asakawa T., Yoshimura Y., Ishisaki A., Tanaka M. “Establishment of immortalized human periodontal ligament cells derived from deciduous teeth”. International Journal of Molecular Medicine, 26:701-705, 2010.
- Yoshida Y., Ito S., Kamo M., Kezuka Y., Tamura H., Kunimatsu K., Kato H. “Production of hydrogen sulfide by two enzymes associated with biosynthesis of homocysteine and lanthionine in Fusobacterium nucleatum subsp. nucleatum ATCC 25586”. Microbiology, 156:2260-2269, 2010.
- Hasegawa T., Chosa N., Asakawa T., Yoshimura Y., Asakawa A., Ishisaki A., Tanaka M. “Effect of fibroblast growth factor-2 on periodontal ligament cells derived from human deciduous teeth in vitro”. Experimental and Therapeutic Medicine, 3:337-341, 2010.
- Hasegawa T., Chosa N., Asakawa T., Yoshimura Y., Asakawa A., Ishisaki A., Tanaka M. “Effect of fibroblast growth factor-2 on dental pulp cells derived from human deciduous teeth in vitro”. Experimental and Therapeutic Medicine, 1:477-480, 2010.
- Okubo N., Ishisaki A., Iizuka T., Tamura M., Kitagawa Y. “Vascular cell-like potential of undifferentiated ligament fibroblasts to construct vascular cell-specific marker-positive blood vessel structures in a PI3K-activation-dependent manner”. Journal of Vascular Research, 47:369-383, 2010.



