A study on the usefulness of human dental pulp cells in hard tissue regeneration

• Project/Area Number: 15K11377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: Nakamura Midori 松本歯科大学, 歯学部, 准教授 (90278177)
• Co-Investigator(Kenkyū-buntansha): 中村 浩志 松本歯科大学, 歯学部, 講師 (00278178) ; 中道 裕子 松本歯科大学, 総合歯科医学研究所, 講師 (20350829) ; 宇田川 信之 松本歯科大学, 歯学部, 教授 (70245801) ; 大須賀 直人 松本歯科大学, 歯学部, 教授 (80247535) ; 溝口 利英 松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 歯髄細胞 / 石灰化 / 骨形成 / 破骨細胞 / 骨芽細胞 / 骨髄細胞 / 骨髄間葉細胞 / BMP-2 / アルカリホスファターゼ / オステオカルシン / リン酸トランスポーター / リバースシグナル / 石灰化メカニズム

Outline of Final Research Achievements

Dental pulp does not calcify in normal tissues. However, when dental pulp fibroblasts were removed from the body and cultured, it was found that the ability to calcify extracellular matrix produced by themselves is higher than that of osteoblasts and bone marrow mesenchymal cells. Cultured pulp fibroblasts possess osteoclastogenesis supporting ability, and the gene expression profile was very similar to osteoblasts and bone marrow mesenchymal cells. In addition, dental pulp fibroblasts were transplanted into immunodeficient mice to form bone with bone marrow. Based on the results of this research, it was possible to clarify the usefulness of pulp fibroblasts as a material in hard tissue regenerative medicine based on the molecular biological characteristics analysis result of pulp fibroblasts.

Research Products

• [Journal Article] The W9 peptide directly stimulates osteoblast differentiation via RANKL signaling. (2017)
  • Author(s): Nakamura M, Nakamichi Y, Mizoguchi T, Koide M, Yamashita T, Ara T, Nakamura H, Penninger JM, Furuya Y, Yasuda H and Udagawa N
  • Journal Title: Journal of Oral Biosciences Volume: 59 Pages: 146-151
• [Journal Article] A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro. (2017)
  • Author(s): Murakami K, Kobayashi Y, Uehara S, Suzuki T, Koide M, Yamashita T, Nakamura M, Takahashi N, Kato H, Udagawa N and Nakamura Y
  • Journal Title: PLOS ONE Volume: 12 Issue: 7 Pages: e0181126-e0181126
  • DOI: 10.1371/journal.pone.0181126
  • Peer Reviewed / Open Access
• [Journal Article] Bone Formation is coupled to resorption via suppression of sclerostin expression by osteoclasts. (2017)
  • Author(s): Koide M, Kobayashi Y, Yamashita T, Uehara S, Nakamura M, Hiraoka BY, Ozaki Y, Iimura T, Yasuda H, Takahashi N and Udagawa N
  • Journal Title: J Bone Mineral Res Volume: 32 Issue: 10 Pages: 2074-2086
  • DOI: 10.1002/jbmr.3175
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling. (2017)
  • Author(s): Uehara S, Udagawa N, Mukai H, Ishihara A, Maeda K, Yamashita T, Murakami K, Nishita M, Nakamura T, Kato S, Minami Y, Takahashi N and Kobayashi Y
  • Journal Title: Sci Signal Volume: 10 Issue: 494
  • DOI: 10.1126/scisignal.aan0023
  • Peer Reviewed / Open Access
• [Journal Article] Angiotensin II stimulation of cardiac hypertrophy and functional decompensation in osteoprotegerin-deficient mice. (2016)
  • Author(s): Tsuruda T, Sekita-Hatakeyama Y, Hao Y, Sakamoto S, Kurogi S, Nakamura M, Udagawa N, Funamoto T, Sekimoto T, Hatakeyama K, Chosa E, Kato J, Asada Y, Kitamura K.
  • Journal Title: Hypertension Volume: 67 Issue: 5 Pages: 848-856
  • DOI: 10.1161/hypertensionaha.115.06689
  • Peer Reviewed / Open Access
• [Journal Article] 歯髄細胞に関する分子生物学的研究 (2016)
  • Author(s): 中道裕子，宇田川信之，高橋直之
  • Journal Title: 腎と骨代謝 Volume: 29 Pages: 31-40
  • NAID: 120006422721
• [Journal Article] The regulation of osteoclast differentiation by Wnt signals (2015)
  • Author(s): Kobayashi Y, Uehara S, Koide M, Takahashi N
  • Journal Title: Bonekey Rep Volume: 4 Issue: 4 Pages: 713-713
  • DOI: 10.1093/jb/mvv124
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dendritic cell-based immunotherapy targeting Wilms' Tumor 1 (WT1) in patients with relapsed malignant glioma. (2015)
  • Author(s): Sakai K, Shimodaira S, Maejima S, Udagawa N, Sano K, Higuchi Y, Koya T, Ochiai T, Koide M, Uehara S, Nakamura M, Sugiyama H, Yonemitsu Y, Okamoto M, Hongo K.
  • Journal Title: J Neurosurg Volume: 123 Issue: 4 Pages: 989-997
  • DOI: 10.3171/2015.1.jns141554
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 大学病院小児歯科における口腔外傷患者実態調査-17年前の受診状況と処置内容の比較 (2015)
  • Author(s): 中村浩志, 溝畑亜紀子, 犬塚勝昭, 中村美どり, 伊藤三智子, 矢ヶ﨑 雅, 大須賀直人
  • Journal Title: 小児歯科学雑誌 Volume: 53 Pages: 406-413
  • NAID: 130005277340
  • Peer Reviewed
• [Journal Article] 破骨細胞による骨破壊性骨吸収と口腔疾患． (2015)
  • Author(s): 中村美どり，小出雅則，中村浩志，宇田川信之
  • Journal Title: CLINICAL CALCIUM Volume: 25 Pages: 1376-1384
• [Journal Article] The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts. (2015)
  • Author(s): Kobayashi Y, Thirukonda GJ, Nakamura Y, Koide M, Yamashita T, Uehara S, Kato H, Udagawa N, Takahashi N
  • Journal Title: J Bone Miner Metab Volume: online
  • Peer Reviewed / Int'l Joint Research
• [Presentation] カテプシンＫ阻害剤投与は、オステオプロテゲリン欠損マウスにおいて、骨吸収抑制と共に骨形成促進作用を示す (2017)
  • Author(s): 中村美どり，中道裕子，溝口利英，小林泰浩，高橋直之，宇田川信之
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] W9 ペプチドのヒト破骨細胞分化抑制作用と骨芽細胞分化促進作用 (2016)
  • Author(s): 歯科基礎医学会学術大会（第58回）
  • Organizer: 中村美どり，小出雅則，山下照仁，小林泰浩，高橋直之，宇田川信之
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2016-08-24
• [Presentation] W9ペプチドのヒト破骨細胞分化抑制機能とヒト骨芽細胞分化促進作用 (2015)
  • Author(s): 中村美どり，宇田川信之
  • Organizer: 第52回日本口腔組織培養学会学術大会
  • Place of Presentation: 徳島大学長井記念ホール（徳島県徳島市）
  • Year and Date: 2015-11-21
• [Presentation] A RANKL-binding peptide W9 inhibits human osteoclast differentiation and stimulates human osteoblast differentiation (2015)
  • Author(s): Nakamura M, Nakamichi Y, Yamashita T, Furuya Y, Yasuda H, Udagawa N
  • Organizer: 米国骨代謝学会（ASBMR）
  • Place of Presentation: ワシントンステートコンベンションセンター（米国ワシントン州）
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] 骨吸収の促進は骨細胞におけるsclerostinの発現を低下させ，Wnt/β-catenin シグナルを促進する (2015)
  • Author(s): 小出雅則，小林泰浩，山下照仁，上原俊介，飯村忠浩，中村美どり，高橋直之，宇田川信之
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-12
• [Presentation] オステオプロテゲリン結合サイトカインであるTRAILの骨組織における役割 (2015)
  • Author(s): 宇田川信之, 中村美どり，中道裕子，小出雅則，小林泰浩，高橋直之
  • Organizer: 第１回日本骨免疫学会
  • Place of Presentation: ブリーズベイマリーナ（沖縄県宮古島市）
  • Year and Date: 2015-06-30
• [Presentation] W9ペプチドのヒト破骨細胞分化抑制作用と骨芽細胞分化促進作用 (2015)
  • Author(s): 中村美どり，中村浩志, 宇田川信之, 山川洋子, 大須賀直人
  • Organizer: 第53回日本小児歯科学会大会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2015-05-21