Asymmetric stem cell division in the homeostasis and the disease onset of periodontal tissue

• Project/Area Number: 24390466
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Shinya 大阪大学, 歯学研究科(研究院), 教授 (70239490) ; YANAGITA Manabu 大阪大学, 歯学研究科(研究院), 助教 (80379081) ; TAKEDACHII Masahide 大阪大学, 歯学研究科(研究院), 助教 (60452447)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 歯周組織幹細胞 / ニッチェ / 非対称性細胞分裂 / ECM蛋白 / 歯根膜細胞 / 幹細胞 / 歯周病 / 歯学

Outline of Final Research Achievements

An asymmetric cell division is crucial for the pool of the tissue stem cells and homeostasis of the organs. To dissect role of the asymmetric stem-cell divisions in the periodontal tissue, we first established the induction model for the senescence in human periodontal ligament (HPDL) cells in the primary culture. HPDL cells showed the decreased ratio of the SSEA3/4,ES cell marker, positive subpopulations depends on the progression of the cell dividing. Trans OMICS approach involving the analysis of transcriptome and proteome identified the global change of profiles in extra cellular matrix (ECM) protein species for the stem-cells exhaustion in senescent HPDL cells. We suggest the proper ECM synthesis is indispensable for the cellular communications in the stem cells/ niches in the homeostasis of periodontal tissue.

Research Products

• [Journal Article] TGF-beta negatively regulates the BMP2-dependent early commitment of periodontal ligament cells into hard tissue forming cells (2015)
  • Author(s): T Kawahara, M Yamashita, K Ikegami, T Nakamura, M Yanagita, S Yamada, M Kitamura, S Murakami
  • Journal Title: PLOS ONE Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isolation and characterization of the human immature osteoblast culture systemf rom the alveolar bones of aged donors for bone regeneration therapy. (2014)
  • Author(s): Aino M, Nishida E, Fujieda Y, Orimoto A, Mitani A, Noguchi T, Makino H,
  • Journal Title: Expert Opin Biol Ther. Volume: 14(12) Issue: 12 Pages: 1731-1744
  • DOI: 10.1517/14712598.2014.960387
  • Peer Reviewed / Open Access
• [Journal Article] Effects of proteasome inhibitor bortezomib on cytodifferentiation and mineralization of periodontal ligament cells (2014)
  • Author(s): J Kitagaki, S Miyauchi1, C Xie, M Yamashita, S Yamada, M Kitamura, S Murakami.
  • Journal Title: J Periodont Res Volume: 50 Issue: 2 Pages: 248-255
  • DOI: 10.1111/jre.12202
  • Peer Reviewed / Open Access
• [Journal Article] Iron plays a key role in the cytodifferentiation of human periodontal ligament cells (2014)
  • Author(s): JX Hou, S Yamada, T Kajikawa, N Ozaki, T Awata, C Fujihara, S Murakami
  • Journal Title: J Periodont Res Volume: 49 Issue: 2 Pages: 260-267
  • DOI: 10.1111/jre.12103
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of a novel periodontal ligament-specific periostin isoform (2014)
  • Author(s): S Yamada, T Tauchi, T Awata, K Maeda, T Kajikawa, M Yanagita, S Murakami
  • Journal Title: J Dent Res Volume: 93 Issue: 9 Pages: 89-95
  • DOI: 10.1177/0022034514543015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Periodontal tissue regeneration by transplantation of adipose tissue-derived multi-lineage progenitor cells (2014)
  • Author(s): M Ozasa, K Sawada, T Iwayama, S Yamamoto, C Morimoto, H Okura, A Matsuyama, H Komoda, C-M Lee, Y Sawa, M Kitamura, T Hashikawa, M Takedachi, S Murakami
  • Journal Title: Inflammation and Regeneration Volume: 34 Pages: 109-116
  • NAID: 130004482326
  • Peer Reviewed
• [Journal Article] Periodontal tissue regeneration by transplantation of adipose tissue–derived stem cells (2013)
  • Author(s): Takedachi M, Sawada K, Yamamoto S, Ozasa M, Shimabukuro Y, Kitamura M, Murakami S
  • Journal Title: Journal of Oral Biosciences Volume: 55 Pages: 137-142
  • Peer Reviewed
• [Journal Article] 歯根膜細胞の石灰化過程におけるTGF-βシグナルの役割 (2013)
  • Author(s): 山下元三、河原貴展、村上伸也
  • Journal Title: 日本歯周病学会会誌 Volume: 55 Pages: 132-139
  • NAID: 10031183908
• [Journal Article] Role of ferritin in the cytodifferentiation of periodontal ligament cells (2012)
  • Author(s): Hou J. Yamada S. Kajikeva T. Ozaki N, Awata T, Yamada S. Murakami S
  • Journal Title: Biochem Biophys Res Commun Volume: 426(4) Pages: 643-648
  • Peer Reviewed
• [Journal Article] Iron plays a key role in the cytodifferentiation of human periodontal ligament cells
  • Author(s): Hou JX, Yamada S, Kajikawa T, Ozaki N, Awata T, Yamada S, Fujihara C, Murakami S
  • Journal Title: Journal of Periodontal Research Volume: (in press)
  • Peer Reviewed
• [Presentation] Cigarette smoke condensate and nicotine exacerbate periodontal tissue destruction in periodontitis-model mouse (2015)
  • Author(s): M Yanagita, M Kubota , K Mori, S Hasegawa, S Yamaba, Motozo Yamashita, S Yamada, M Kitamura, S Murakami
  • Organizer: 2015 IADR/AADR/CADR General Session & Exhibition
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-12
• [Presentation] Hypoxia Regulates PLAP-1 Expression in Periodontal Ligament Cells (2015)
  • Author(s): S Yamamoto, M Takedachi, C Morimoto, T Awata, S Yamaba, S Yamada, S Murakami
  • Organizer: 2015 IADR/AADR/CADR General Session & Exhibition
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-12
• [Presentation] Analysis of cellular senescence in aged human periodontal ligament cells (2014)
  • Author(s): K Ikegami, M Yamashita, T Nakamura, M Kubota, K Mori, M Yanagita, M Kitamura S Murakami
  • Organizer: AAP 100th Anniversary Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-09-20
• [Presentation] AUTOPHAGY REGULATES EXTRACELLULAR MATRIX PRODUCTION BY HUMAN PERIODONTAL LIGAMENT CELLS (2014)
  • Author(s): M Yamashita, T Nakamura, K Ikegami, S Yamaba, M Kubota, K Mori, M Yanagita, T Nozaki, M Kitamura, S Murakami
  • Organizer: AAP 100th Anniversary Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-09-20
• [Presentation] Periodontal Tissue engineering by FGF-2 (2014)
  • Author(s): S Murakami
  • Organizer: International Association for Dental Research (IADR) General Session
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2014-06-25
  • Invited
• [Presentation] Periodontal tissue regeneration by cytokine therapy and stem-cell therapy (2013)
  • Author(s): S Murakami
  • Organizer: The 6th Pan Pacific Symposium on Stem Cells and Cancer Research.
  • Place of Presentation: Hsinchu Taiwan
  • Invited
• [Presentation] FGF-2・脂肪組織由来幹細胞を用いた歯周組織再生療法 (2013)
  • Author(s): 村上伸也
  • Organizer: 第67回日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
  • Invited
• [Presentation] ヒト歯根膜細胞のSASP（Senescence-associated secretory phenotype）の解析 (2013)
  • Author(s): 山下元三、池上久仁子、山田聡、北村正博、村上伸也
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 兵庫（神戸国際会議場）
• [Presentation] Analysis of SASP (senescence-associated secretory phenotype) in periodontal ligament (2013)
  • Author(s): K Ikegami, M Yamashita, T Nakamura, M Yanagita, S Yamada, M Kitamura, S Murakami
  • Organizer: 2nd Meeting of the International Association for Dental Research &; Asia Pacific Region
  • Place of Presentation: Bangkok, Thailand (Plaza Athenee,バンコク,タイ)
• [Presentation] Effect of aging on a hard tissue-forming ability of periodontal ligament cells. (2012)
  • Organizer: 第60回国際歯科研究学会日本部会(JADR)
  • Place of Presentation: 新潟市
  • Year and Date: 2012-12-14