Establishment of the next-generation intentional replantation by using of Wnt5a signaling-induced effective periodontal ligament tissue regeneration

• Project/Area Number: 16K20458
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Conservative dentistry
• Research Institution: Kyushu University
• Principal Investigator: Hasegawa Daigaku 九州大学, 大学病院, 助教 (20757992)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 歯根膜 / Wnt5a / Ror2 / JNK / コラーゲン線維形成促進 / 石灰化抑制 / ヒト歯根膜細胞 / 線維形成 / 歯根膜幹細胞

Outline of Final Research Achievements

In this study, it was revealed that Wnt5a acts on promoting the collagen-formation and suppression of the calcification in human periodontal ligament（PDL）cells via Ror2 and JNK. It was also shown that Ror2 is highly expressed in human PDL cell line with high expression of PDL-related markers. These results suggest that Wnt5a/Ror2/JNK signaling is involved in the mechanism by which PDL tissue maintains fibrous connective tissue without calcification.

Research Products

• [Journal Article] Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells (2018)
  • Author(s): Hamano Sayuri、Tomokiyo Atsushi、Hasegawa Daigaku、Yoshida Shinichiro、Sugii Hideki、Mitarai Hiromi、Fujino Shoko、Wada Naohisa、Maeda Hidefumi
  • Journal Title: Stem Cells and Development Volume: 27 Issue: 2 Pages: 100-111
  • DOI: 10.1089/scd.2017.0077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2/JNK signaling (2017)
  • Author(s): Hasegawa Daigaku、Wada Naohisa、Yoshida Shinichiro、Mitarai Hiromi、Arima Mai、Tomokiyo Atsushi、Hamano Sayuri、Sugii Hideki、Maeda Hidefumi
  • Journal Title: Journal of Cellular Physiology Volume: 233 Issue: 2 Pages: 1752-1762
  • DOI: 10.1002/jcp.26086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transgelin mediates transforming growth factor-β1-induced proliferation of human periodontal ligament cells (2017)
  • Author(s): Mitarai H.、Wada N.、Hasegawa D.、Yoshida S.、Sonoda M.、Tomokiyo A.、Hamano S.、Serita S.、Mizumachi H.、Maeda H.
  • Journal Title: Journal of Periodontal Research Volume: 52 Issue: 6 Pages: 984-993
  • DOI: 10.1111/jre.12466
  • Peer Reviewed / Open Access
• [Journal Article] Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells (2017)
  • Author(s): Mizumachi Hiroyuki、Yoshida Shinichiro、Tomokiyo Atsushi、Hasegawa Daigaku、Hamano Sayuri、Yuda Asuka、Sugii Hideki、Serita Suguru、Mitarai Hiromi、Koori Katsuaki、Wada Naohisa、Maeda Hidefumi
  • Journal Title: Bone Volume: 101 Pages: 191-201
  • DOI: 10.1016/j.bone.2017.05.012
  • Peer Reviewed / Open Access
• [Journal Article] Glial cell line-derived neurotrophic factor from human periodontal ligament cells treated with proinflammatory cytokines promotes neurocytic differentiation of PC12 cells. (2017)
  • Author(s): Yoshida S, Yamamoto N, Wada N, Tomokiyo A, Hasegawa D, Hamano S, Mitarai H, Monnouchi S, Yuda A, Maeda H.
  • Journal Title: J Cell Biochem. Volume: 118 Issue: 4 Pages: 699-708
  • DOI: 10.1002/jcb.25662
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transforming growth factor-β-induced gene product-h3 inhibits odontoblastic differentiation of dental pulp cells. (2017)
  • Author(s): 芹田俊、友清淳、長谷川大学、濱野さゆり、杉井英樹、吉田晋一郎、水町博之、御手洗裕美、門野内聡、和田尚久、前田英史
  • Journal Title: Archives of oral biology Volume: 78 Pages: 135-143
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Semaphorin 3A Induces Odontoblastic Phenotype in Dental Pulp Stem Cells. (2016)
  • Author(s): Yoshida S, Wada N, Hasegawa D, Miyaji H, Mitarai H, Tomokiyo A, Hamano S, Maeda H.
  • Journal Title: Journal of Dental Research Volume: 95 Issue: 11 Pages: 1282-1290
  • DOI: 10.1177/0022034516653085
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Tenomodulinがヒト歯根膜細胞の機能維持に及ぼす影響について (2017)
  • Author(s): 長谷川大学、和田尚久、有馬麻衣、吉田晋一郎、友清淳、濱野さゆり、御手洗裕美、前田英史
  • Organizer: 第146回日本歯科保存学会春季学術大会
• [Presentation] R-spondin2はカノニカルWntシグナルを介して未分化なヒト歯根膜細胞の骨芽細胞様分化を促進する (2017)
  • Author(s): 有馬麻衣、長谷川大学、吉田晋一郎、御手洗裕美、友清淳、濱野さゆり、杉井英樹、和田尚久、前田英史
  • Organizer: 第147回日本歯科保存学会周期学術大会
• [Presentation] ヒト歯根膜幹細胞における新規幹細胞特性制御因子としてのMESTの可能性 (2017)
  • Author(s): 長谷川大学、御手洗裕美、長谷川佳那、有馬麻衣、濱野さゆり、吉田晋一郎、友清淳、杉井英樹、和田尚久、清島保、前田英史
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] R-spondin2がヒト歯根膜幹細胞の線維芽細胞様分化に及ぼす影響について (2016)
  • Author(s): 園田麻衣、長谷川大学、和田尚久、吉田晋一郎、御手洗裕美、友清淳、濱野さゆり、前田英史
  • Organizer: 第145回日本歯科保存学会
  • Place of Presentation: キッセイ文化ホール（長野県松本文化会館）
  • Year and Date: 2016-10-27
• [Presentation] Identification of a novel periodontal ligament stem cell marker (2016)
  • Author(s): 長谷川大学、和田尚久、濱野さゆり、友清淳、吉田晋一郎、御手洗裕美、園田麻衣、杉井英樹、前田英史
  • Organizer: 94th General Session & Exhibition of the IADR
  • Place of Presentation: CoEx Convention & Exhibition Center
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] MESTはヒト歯根膜幹細胞における幹細胞特性の維持に関与する (2016)
  • Author(s): 長谷川大学、和田尚久、濱野さゆり、友清淳、吉田晋一郎、御手洗裕美、園田麻衣、杉井英樹、前田英史
  • Organizer: 第144回日本歯科保存学会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2016-06-09