Ubiquitin-proteasome system regulates cytokine signal crosstalk in periodontal stem cells

• Project/Area Number: 21689053
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Periodontal dentistry
• Research Institution: Osaka University
• Principal Investigator: YAMASHITA Motozo 大阪大学, 歯学部附属病院, 助教 (90524984)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000); Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2010: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 歯学 / シグナル伝達 / 歯周外科学 / シグナルクロストーク / ユビキチン化システム

Research Abstract

In this study, we investigated the cross talk mechanism of intracellular signaling induced by multiple growth factors in periodontal stem cells. We found TGF-βwas crucial for commitment to pre-osteoblast lineage from periodontal ligament cells and ECM production in the presence of BMP2. DNA chip analysis revealed the Smurfs, Ski and Smad7, ubiquitin-proteasome system related genes, as the key determinants for cytodifferentiation to the calcified nodule forming cells.

Research Products

• [Journal Article] A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20 (2012)
  • Author(s): Blank M, Tang Y, Yamashita M, Burkett SS, Cheng SY, Zhang YE
  • Journal Title: Nat Med Volume: 18(2) Pages: 227-234
  • Peer Reviewed
• [Journal Article] Ablation of Smurf2 reveals an inhibition in TGF-βsignalling through multiple mono-ubiquitination of Smad3 (2011)
  • Author(s): Tang LY, Yamashita M, Coussens NP, Tang Y, Wang X, Li C, Deng CX, Cheng SY, Zhang YE
  • Journal Title: EMBO J Volume: 30(23) Pages: 4777-4789
  • Peer Reviewed
• [Journal Article] A negative feedback control of TGF-beta signaling by GSK3-mediated Smad3 linker phosphorylation at Ser204 (2009)
  • Author(s): 山下元三
  • Journal Title: J Biol Chem. 284(30) Pages: 19808-19816
  • Peer Reviewed
• [Presentation] Ossification of periodontal ligament cells induced by TGF-βtype I receptor inhibitor (2011)
  • Author(s): T. KAWAHARA, M. YAMASHITA, and S. MURAKAMI
  • Organizer: Osaka International Symposium" Current Topics on Frontier Oral Science
  • Place of Presentation: Osaka
  • Year and Date: 2011-11-24
• [Presentation] TGF-βI型受容体阻害剤による歯根膜細胞の石灰化制御 (2011)
  • Author(s): T.KAWAHARA, M.YAMASHITA, S.MURAKAMI
  • Organizer: Osaka International Symposium "Current Topics on Frontier Oral Science
  • Place of Presentation: Osaka
  • Year and Date: 2011-11-24
• [Presentation] SIRT1による歯根膜細胞の石灰化制御 (2011)
  • Author(s): 中村友美, 山下元三, 河原貴展, 橋本悠平, 梶川哲宏, 森健太, 前田憲一郎, 北垣次郎太, 柳田学, 山田聡, 北村正博, 村上伸也
  • Organizer: 日本歯科保存学会2011年度秋季学術大会(第135回)
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-21
• [Presentation] Dual mode of TGF-βfunction in periodontal ligamental cell calcification (2011)
  • Author(s): T. KAWAHARA, M. YAMASHITA, T. Nakamura, T. KAJIKAWA, S. YAMADA, M. KITAMURA and S. MURAKAMI
  • Organizer: The 59th Annual Meeting of Japanese Association of Dental Research
  • Place of Presentation: Hiroshima
  • Year and Date: 2011-10-09
• [Presentation] 歯根膜細胞においてFGF-2はWnt依存性にBMPシグナルを制御する (2011)
  • Author(s): 山下元三、河原貴展、橋本悠平、中村友美、梶川哲宏、森健太、前田憲一郎、北垣次郎太、柳田学、山田聡、北村正博、村上伸也
  • Organizer: 日本歯科保存学会2011年度春季学術大会(第134回)
  • Place of Presentation: 東京
  • Year and Date: 2011-06-10
• [Presentation] Endogenous TGF-βdownregulates mineralization of periodontal ligament cells in vitro (2011)
  • Author(s): 河原貴展、山下元三、橋本悠平, 中村友美, 梶川哲宏, 前田憲一郎, 北垣次郎太, 山田聡, 北村正博, 村上伸也
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-03
• [Presentation] Endogenous TGF-β downregulates mineralization of periodontal ligament cells in vitro (2011)
  • Author(s): 河原貴展、山下元三、橋本悠平,中村友美, 梶川哲宏, 前田憲一郎, 北垣次郎太, 山田聡, 北村正博, 村上伸也
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-03
• [Presentation] 歯根膜細胞におけるオートファジーの役割 (2011)
  • Author(s): 中村友美, 山下元三, 河原貴展, 橋本悠平, 梶川哲宏, 山田聡, 北垣次郎太, 前田憲一郎, 北村正博, 村上伸也
  • Organizer: 第54回春季日本歯周病学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-05-28
• [Presentation] Post-transcriptional control of BMPsignaling by FGF-2 in periodontal ligament cells (2011)
  • Author(s): Y. HASHIMOTO, M. YAMASHITA, T. KAWAHARA, T. NAKAMURA, T. KAJIKAWA, S. YAMADA, T. NOZAKI, M. KITAMURA, and S. MURAKAMI
  • Organizer: 89th General Session & Exhibition of the IADR
  • Place of Presentation: San Diego, CA
  • Year and Date: 2011-03-19
• [Presentation] Endogenous TGF-βdownregulates mineralization of periodontal ligament cells in vitro (2011)
  • Author(s): T. KAWAHARA, M. YAMASHITA, Y. HASHIMOTO, T. NAKAMURA, T. KAJIKAWA, S. YAMADA, M. KITAMURA, and S. MURAKAMI
  • Organizer: 89th General Session & Exhibition of the IADR
  • Place of Presentation: San Diego, CA
  • Year and Date: 2011-03-18
• [Presentation] FGF-2-MAPK signal pathway suppresses BMP signaling axis in periodontal ligament cells (2010)
  • Author(s): T. Kawahara and M. YAMASHITA
  • Organizer: Osaka-Chulalongkorn-Mahidol Joint Symposium," Current topics on Oral Science"
  • Place of Presentation: Osaka
  • Year and Date: 2010-11-26
• [Presentation] FGF-2-MAPK signal pathway suppresses BMP signaling axis in periodontal ligament cells (2010)
  • Author(s): 山下元三、河原貴展
  • Organizer: Osaka-Chulalongkorn-Mahidol Joint Symposium
  • Place of Presentation: Osaka
  • Year and Date: 2010-11-26
• [Presentation] TGF-βsignaling regulates mineralization of periodontal ligament cells. (2010)
  • Author(s): T. KAWAHARA, M. YAMASHITA, Y. HASHIMOTO, T. KAJIKAWA, S. YAMADA, M. KITAMURA, and S. MURAKAMI
  • Organizer: The 96th Annual Meeting of American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Honolulu, Hawai
  • Year and Date: 2010-10-30
• [Presentation] 歯根膜細胞においてFGF-2はMAPK依存性にBMPシグナルを抑制する (2010)
  • Author(s): 河原貴展、山下元三、橋本悠平、梶川哲宏、中村友美, 前田憲一郎、山田聡、北村正博、村上伸也
  • Organizer: 第53回秋季日本歯周病学会学術大会
  • Place of Presentation: 高松
  • Year and Date: 2010-09-19
• [Presentation] 歯根膜細胞においてFGF-2はMAPK依存性にBMPシグナルを抑制する (2010)
  • Author(s): 山下元三、河原貴展
  • Organizer: 第53回日本歯周病学会秋季学術大会
  • Place of Presentation: 高松
  • Year and Date: 2010-09-19
• [Presentation] FGF-2はMAPK依存性にBMPによるSmad1リン酸化を抑制する (2010)
  • Author(s): 山下元三、河原貴展
  • Organizer: 日本歯科保存学会2010年度春季学術大会(第132回)
  • Place of Presentation: 熊本
  • Year and Date: 2010-06-04
• [Presentation] TGF-β signaling regulates mineralization of periodontal ligament cells (2010)
  • Author(s): 山下元三、河原貴展
  • Organizer: The 96th Annual Meeting of American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Honolulu, Hawaii
• [Presentation] A negative feedback control of TGF-beta signaling by GSK3-mediated Smad3 linker phosphorylation at Ser204 (2009)
  • Author(s): 山下元三
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] TGF-βI型受容体阻害剤による歯根膜細胞の石灰化制御 (2009)
  • Author(s): 河原貴展、山下元三、梶川哲宏、橋本悠平、柳田学、山田聡、北村正博、村上伸也
  • Organizer: 日本歯科保存学会2009年度秋季学術大会(第131回)
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-29
• [Presentation] FGF-2はMAPK依存性にBMPによるSmad1リン酸化を抑制する (2009)
  • Author(s): 河原貴展、山下元三、橋本悠平、梶川哲宏、前田憲一郎、北垣次郎太、山田聡、北村正博、村上伸也
  • Organizer: 日本歯科保存学会2010年度春季学術大会(第132回)
  • Place of Presentation: 熊本
  • Year and Date: 2009-06-04