Differentiation mechanism of cell proliferation, migration, adn differntiation in the oral proliferative lesions

• Project/Area Number: 17K11862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: KAWAKAMI Toshiyuki 松本歯科大学, 総合歯科医学研究所, 特任教授 (80104892)
• Co-Investigator(Kenkyū-buntansha): 富田 美穂子 松本歯科大学, 歯学部附属病院, 教授 (00366329) ; 前田 初彦 愛知学院大学, 歯学部, 教授 (30175591) ; 長塚 仁 岡山大学, 医歯薬学総合研究科, 教授 (70237535)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 歯周組織 / 骨髄幹細胞 / 組織幹細胞 / 慢性炎症 / 肉芽腫性炎 / 腫瘍 / 細胞分化 / HSP / 肉芽腫性炎症 / 細胞増殖 / 骨髄間葉系細胞 / 口腔 / 歯原生 / 創傷治癒 / 免疫組織化学 / 歯原性腫瘍 / 異物肉芽腫 / 歯根膜ポリープ / Wnt / Notch / 病理学 / 細胞・組織 / 再生医学 / 癌 / 発生分化

Outline of Final Research Achievements

Our experimental data the remodeling of the PDL with cell acceleration at the furcation area in this experimental model recovered using the cells in situ and the bone-marrow-derived cells (BMCs). BMC migration into the PDL tissues using Green Fluorescent Protein (GFP) bone marrow transplanted model mouse was examined. BMCs have abilities of cell migration and differentiation into tissues/organs in the body. The immunohistochemistry revealed that GFP positive cells were detected in these legions. Further, experimentally induced periodontal polyp cells are mainly from migration of undifferentiated mesenchymal cells of the bone marrow, and differentiate into the tissue-specified cells. Furthermore, regarding odontogenic tumor tissues, especially ameloblastoma cells, Wnt- Notch-signaling involvements, and/or HSP (pHSP) suggest to relation the cell differentiation of the tissue specific differentiations, especially of squamous cell metaplasia of the tumor cell nests.

Academic Significance and Societal Importance of the Research Achievements

口腔領域では，骨髄幹細胞を用いる再生医療研究は骨組織の再建等極めて限られた領域での報告があるのみであり，今後の発展が見込まれる分野である。口腔外科領域における各種細胞増殖性病変，すなわち歯原性腫瘍，唾液腺腫瘍，およびその間質細胞などの細胞供給に関わる研究領域のほか，歯周組織の改造現象，さらには歯槽膿瘍，歯根肉芽腫，膿瘍などの歯根端部の慢性炎症性病変などにおける細胞増殖性病変の場においても，その治癒を促進させるための過程には骨髄幹細胞の関与があると推察されるので，骨髄幹細胞の機能解明を行う生物学的意義は大きい。効果的な新規の増殖性病変に対する増殖抑制など治療法の開発に繋がるであろう。

Research Products

• [Journal Article] Wnt signaling and histological characteristics of odontogenic tumors. (2020)
  • Author(s): Nakano K, Takabatake K, Kawai H, Yoshida S, Maeda H, Kawakami T and Nagatsuka H.
  • Journal Title: Daig Pathol Open Volume: 5(1) Pages: 160-160
  • Peer Reviewed / Open Access
• [Journal Article] Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics (2019)
  • Author(s): Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Yoshida Saori、Maeda Hatsuhiko、Kawakami Toshiyuki、Nagatsuka Hitoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 8 Pages: 1973-1973
  • DOI: 10.3390/ijms20081973
  • NAID: 120006765095
  • Peer Reviewed / Open Access
• [Journal Article] The role of bone marrow-derived cells during ectopic bone formation of mouse femoral muscle in GFP mouse bone marrow transplantation model. (2018)
  • Author(s): Takabatake K, Tsujigiwa H, Song Y, Matsuda H, Kawai H, Fujii M, Hamada M, Nakano K, Kawakami T and Nagatsuka H.
  • Journal Title: Int J Med Sci Volume: 15 Issue: 8 Pages: 748-757
  • DOI: 10.7150/ijms.24605
  • Peer Reviewed / Open Access
• [Journal Article] Cell supplying to the experimentally induced absorbable suture thread foreign body granuloma from the bone marrow tissues. (2018)
  • Author(s): Nakayasu Y, Aoki S, Shoumura M, Osuga N, Okafuji N, Nakano K, Nagatsuka H, Tsujigiwa H and Kawakami T.
  • Journal Title: Int J Dent Oral Sci Volume: 5 Pages: 641-644
  • DOI: 10.19070/2377-8075-18000126
  • Peer Reviewed / Open Access
• [Journal Article] Signaling dinamics in cell differentiation of pleomorphic adenomas. (2018)
  • Author(s): Yoshida W, Sugita Y, Isomura M, Kawai R, Kubo K, Maeda H, Ueda Y, Nakano K, Nagatsuka H and Kawakami T.
  • Journal Title: J Dent Oral Health Volume: 4
  • Peer Reviewed / Open Access
• [Journal Article] Pathological analysis on tissue reactions to absorbable monofilament suture -using GFP bone marrow transplaｎted rat model -. (2018)
  • Author(s): Nakayasu Y, Aoki S, Shoumura M, Osuga N, Okafuji N, Nakano K, Nagatsuka H, Tsujigiwa H and Kawakami T.
  • Journal Title: J Dent Oral Health Volume: 4
  • Peer Reviewed / Open Access
• [Journal Article] HSP47 as a Possible Molecular Chaperone for the collagen synthesis in the Mouse Periodontal Ligament Cells due to Orthodontic Force (2017)
  • Author(s): Muraoka R, Nakano K, Yamada K, Kawakami T
  • Journal Title: Int J Dentistry Oral Sci. Volume: ４（1） Pages: 387-394
  • DOI: 10.19070/2377-8075-1700078
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reactions to Bioabsorbable Suture Thread Embedded in Rat Subcutaneous Tissue (2017)
  • Author(s): Nakayasu Y, Matsuda S, Moriyama K, Okafuji N, Mizohata A, Shoumura M, Kawakami T and Osuga N
  • Journal Title: Journal of Hard Tissue Biology Volume: 26 Issue: 3 Pages: 281-284
  • DOI: 10.2485/jhtb.26.281
  • NAID: 130005745399
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed
• [Journal Article] Overview of Cytological Dynamics of Periodontal Ligament Inflammatory Lesions. (2016)
  • Author(s): Matsuda S, Nakano K, Tsujigiwa H, Takabatake K, Okafuji N, Shoumura M, Osuga N, Nagatsuka H and Kawakami T
  • Journal Title: Int J Dent Oral Sci Volume: S9 Pages: 1-7
  • DOI: 10.19070/2377-8075-si09001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 頭頸部領域再建におけるハニカムTCPの硬組織再生メカニズム解明と臨床応用の検討． (2019)
  • Author(s): 高畠清文，辻極秀次，河合穂高，吉田沙織，大森悠加，中野敬介，川上敏行，長塚 仁．
  • Organizer: 硬組織再生生物学会総会（29回）2019年8月23-24日，札幌
• [Presentation] コレステリン肉芽腫における骨髄由来免疫抑制細胞（MDSC）の免疫組織化学的検討． (2019)
  • Author(s): 中野敬介，河合穂高，髙畠清文，吉田沙織，大森悠加，長塚 仁，川上敏行．
  • Organizer: 硬組織再生生物学会総会（29回）2019年8月23-24日，札幌
• [Presentation] 実験的に誘発させたコレステリン肉芽腫における細胞分化の病理学的解析 (2018)
  • Author(s): 中野敬介，川上敏行，辻極秀次，長塚 仁
  • Organizer: 日本病理学会総会（第107回）
• [Presentation] Cell supplying into the experimentally induced foreign body granuloma from the bone marrow mesenchymal cells. (2018)
  • Author(s): Kawakami T, Shoumura M, Matsuda S, Moriyama K, Nakano K, Tsujigiwa H, Nagatsuka H and Osuga N.
  • Organizer: Asia Pacific Congress on Dental and Oral Health (32nd)
  • Int'l Joint Research
• [Presentation] Possible role of Notch signaling in the cells from migration of the bone marrow mesenchymal cells experimentally induced periodontal inflammatory lesions using GFP BMT-model mice. (2018)
  • Author(s): Shoumura M, Matsuda S, Moriyama K, Kida A, Osuga N, Okafuji N, Nakano K, Tsujigiwa H and Kawakami T
  • Organizer: Asia Pacific Congress on Dental and Oral Health (32nd)
  • Int'l Joint Research
• [Presentation] 吸収性縫合糸 Vicryl® とVicryl Rapide®に対する異物反応の相違 －GFP骨髄移植ラットを用いての検討－． (2018)
  • Author(s): 中安喜一，青木紗衣佳，正村正仁，大須賀直人，岡藤範正，辻極秀次，中野敬介，長塚 仁，川上敏行．
  • Organizer: 硬組織再生生物学会総会（28回）
• [Presentation] 吸収性縫合糸 Vicrylに対するGFP骨髄移植ラットにおける皮下組織の反応． (2018)
  • Author(s): 中野敬介，中安喜一，正村正仁，大須賀直人，辻極秀次，長塚 仁，川上敏行．
  • Organizer: 歯科基礎医学会総会（60回）
• [Presentation] エナメル上皮における Heat Shock Protein27 の発現と細胞分化． (2018)
  • Author(s): 上田優貴子，中野敬介，吉田和加，杉田好彦，久保勝俊，前田初彦，長谷川博雅，川上敏行．
  • Organizer: 日本口腔外科学会総会（63回）
• [Presentation] エナメル上皮線維腫における Wntとβ-cateninの発現 (2017)
  • Author(s): 中野敬介，髙畠清文，杉田好彦，久保勝俊，前田初彦，川上敏行，長塚 仁
  • Organizer: 日本病理学会総会（第106回）
• [Presentation] マウス臼歯の髄床底穿孔による歯根膜ポリープ形成における細胞の移動と分化 (2017)
  • Author(s): 松田紗衣佳，辻極秀次，中野敬介，岡藤範正，正村正仁，大須賀直人，川上敏行
  • Organizer: 日本外傷歯学会総会・学術大会（第17回）
• [Presentation] Cell differentiation due to Wnt signaling in ameloblastic fibromas (2017)
  • Author(s): Kawakami T, Nakano K, Ueda Y, Takabatake K, Yoshida W, Sugita Y, Kubo K, Maeda H and Nagatsuka H
  • Organizer: Asia Pacific Congress & Expo on Dental and Oral Health (28th)
  • Int'l Joint Research
• [Presentation] 歯根膜における骨髄由来未分化間葉細胞の局所特有の線維芽細胞への分化 (2017)
  • Author(s): 松田紗衣佳，辻極秀次，中野敬介，岡藤範正，長塚 仁，正村正仁，大須賀直人，川上敏行
  • Organizer: 硬組織再生生物学会総会（27回）
• [Presentation] 吸収性縫合糸Vicrylに対するラット皮下組織の反応 (2017)
  • Author(s): 中安喜一，松田紗衣佳，森山敬太，岡藤範正，正村正仁，大須賀直人，川上敏行
  • Organizer: 硬組織再生生物学会総会（27回）
• [Presentation] マウス臼歯の髄床底穿孔による歯根膜ポリープ形成における細胞の移動と分化 (2017)
  • Author(s): 松田紗衣佳, 正村正仁，大須賀直人, 中野敬介, 辻極秀次, 長塚 仁, 川上敏行
  • Organizer: 日本口腔科学会中部地方部会
• [Presentation] 吸収性縫合糸 Vicryl® をラット皮下組織内に埋入した時に出現する異物肉芽腫 (2017)
  • Author(s): 中安喜一，松田紗衣佳，森山敬太，正村正仁，辻極秀次，中野敬介，長塚 仁，大須賀直人，川上敏行
  • Organizer: 日本口腔科学会中部地方部会
• [Presentation] ラットの皮下組織内に埋入した吸収性縫合糸Vicrylに対し出現するマクロファージ (2017)
  • Author(s): 中安喜一，松田紗衣佳，森山敬太，正村正仁，辻極秀次，中野敬介，長塚 仁，大須賀直，川上敏行
  • Organizer: 歯科基礎医学会総会（59回）
• [Presentation] 骨髄由来細胞の歯根膜ポリープにおける局所特有の線維芽細胞への移動と分化 (2017)
  • Author(s): 松田紗衣佳，正村正仁，大須賀直人，辻極秀次，中野敬介，川上敏行
  • Organizer: 歯科基礎医学会総会（59回）
• [Presentation] マウス歯周組織改造における骨髄間葉系細胞の移動と分化 (2017)
  • Author(s): 金子圭子，辻極秀次，松田紗衣佳，中野敬介，村岡理奈，長塚 仁，川上敏行
  • Organizer: 歯科基礎医学会総会（59回）
• [Presentation] メカニカルストレスが惹起するHSP70 によるマウス歯根膜の修復 (2017)
  • Author(s): 村岡理奈，中野敬介，山田一尋，川上敏行
  • Organizer: 歯科基礎医学会総会（59回）
• [Presentation] エナメル上皮線維腫における Wntシグナルと細胞分化 (2017)
  • Author(s): 上田優貴子，中野敬介，髙畠清文，吉田和加，杉田好彦，久保勝俊，前田初彦，長塚 仁，川上敏行
  • Organizer: 日本口腔外科学会総会（62回）
• [Book] Involvement of heat shock proteins during periodontal ligament remodeling. Chapter 3: 51-70, In Periodontology, ed by Jane Manakil (2019)
  • Author(s): Muraoka R, Nakano K, Tsujigiwa H, Nagatsuka H, Matsuda H, Tomida M, Okafuji N, Yamada K and Kawakami T.
  • Total Pages: 20
  • Publisher: InTechOpen Ltd., London, UK,
• [Book] Bone marrow mesenchymal cell contribution in maintenance of periodontal ligament homeostasis. Chapter 6: 93-110, In Histology, ed by Thomas Heinbocked and Vonnie DC Shields (2019)
  • Author(s): Kawakami T, Kaneko K, Takaya T, Aoki S, Muraoka R, Tomida M, Okafuji N, Shoumura M, Osuga N, Nakano K, Tsujigiwa H and Nagatsuka H.
  • Total Pages: 17
  • Publisher: InTechOpen Ltd., London, UK,
  • ISBN: 9789535167983
• [Book] Histology, Chanper 6 (2019)
  • Author(s): Kawakami T, Kaneko K, Takaya T, Aoki S, Muraoka R, Tomida M, Okafuji N, Shoumura M, Osuga N, Nakano K, Tsujigiwa H and Nagatsuka H.
  • Total Pages: 18
  • Publisher: InTechOpen, London, UK
• [Book] Periodontology and Dental Implantology, Chapter 3 (2019)
  • Author(s): Muraoka R, Nakano K, Tsujigiwa H, Nagatsuka H, Matsuda H, Tomida M, Okafuji N, Yamada K and Kawakami T.
  • Total Pages: 20
  • Publisher: InTechOpen, London, UK
• [Book] Advances in Medicine and Biology, Vol 111. Berhardt LV ed., (2017)
  • Author(s): Kawakami T, Tsujigiwa H, Takaya T, Kaneko K, Mimura H, Matsuda S, Muraoka R, Tomida M, Okafuji N, Fujii T, Nakano K and Nagatsuka H
  • Publisher: Nova Biomedical Publisher, NY, USA
  • ISBN: 9781536105131
• [Book] Medicine Research Summaries, Vol 20 (2017)
  • Author(s): Kawakami T, Tsujigiwa H, Takaya T, Kaneko K, Mimura H, Matsuda S, Muraoka R, Tomida M, Okafuji N, Fujii T, Nakano K and Nagatsuka H
  • Publisher: Nova Biomedical Publisher, NY, USA
  • ISBN: 9781536129663