Direct reprogramming to osteocytes by modulating insulator function

• Project/Area Number: 24659870
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IKEDA Masa-Aki 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (20193211)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 分化転換 / リプログラミング / インスレーター / 骨細胞 / ARID3A / 繊維芽細胞 / 間葉系幹細胞 / 再生医療 / 骨 / 軟骨 / 培養 / 脂肪 / siRNA

Outline of Final Research Achievements

In this study, we tried to inhibit insulator functions by siRNA-mediated ARID3A silencing and thereby facilitate reprogramming. In order to convert human fibroblasts into osteocytes, we tested the effects of siRNA-mediated ARID3Asilencing and various combinations of small chemical compounds and growth factors on epigenetic reprogramming of fibroblasts. We found a combination of small chemical compounds and growth factors that directly converted fibroblasts into osteocytes and adipocytes without using siRNA-mediated ARID3A silencing.

Research Products

• [Journal Article] Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells (2014)
  • Author(s): 3.Yuniardini S Wimardhani, Dewi F Suniarti, Hans J Freisleben, Septelia I Wanandi, Nurjati C Siregar, Masa-Aki Ikeda
  • Journal Title: Journal of Oral Science Volume: 56 Issue: 2 Pages: 119-126
  • DOI: 10.2334/josnusd.56.119
  • NAID: 130004479925
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Apoptotic Activities of Thymoquinone, an Active Ingredient of Black Seed (Nigella sativa), in Cervical Cancer Cell Lines (2014)
  • Author(s): 2.Ichwan SJ, Al-Ani IM, Bilal HG, Suriyah WH, Taher M, Ikeda MA
  • Journal Title: Chin. J Physiol. Volume: 57 Issue: 5 Pages: 249-255
  • DOI: 10.4077/cjp.2014.bab190
  • Peer Reviewed
• [Journal Article] Expression of p27Kip1 and E-cadherin in Head and Neck Squamous Cell Carcinoma of Indonesian Patients. (2014)
  • Author(s): 1.Auerkari EI, Joewono V, Handjari DR, Sarwono1 AT, Suhartono AW, Eto K, Ikeda MA
  • Journal Title: Open Dentistry J Volume: 8 Issue: 1 Pages: 136-143
  • DOI: 10.2174/1874210601408010136
  • Peer Reviewed / Open Access
• [Journal Article] Chitosan Exhibites Anticancer Activity Through Induction of Apoptosis and Cell Cycle Arrest in Oral Cancer Cells (2014)
  • Author(s): Wimardhani SY, Suniarti DF, Freisleben HJ, Wanandi SI, Siregar NC, Ikeda MA
  • Journal Title: Journal of Oral Science Volume: in press
  • Peer Reviewed
• [Journal Article] FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. (2012)
  • Author(s): 1. Chung YM, Park S-H, Tsai W-B, Wang S-Y, Ikeda MA, Berek JS, Chen DJ, Hu MC
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1000-1000
  • DOI: 10.1038/ncomms2008
  • Peer Reviewed
• [Presentation] Maintenance of Stemness in Mesenchymal Stem Cells during Long-Term Culture (2014)
  • Author(s): Zhang Kui, Shohei Kasugai, Masa-Aki Ikeda
  • Organizer: 第79回口腔病学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-05 – 2014-12-06
• [Presentation] Critical roles for ARID3B in Expression of Proapoptotic p53-Target Genes and Cell Death Following DNA Damage (2014)
  • Author(s): Endrawan Pratama, Sachiko Iseki, Masa-Aki Ikeda
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Immunohistochemical detection of cyclin E in non-proliferating neurons of the mouse adult hippocampal dentate gyrus (2014)
  • Author(s): Ikeda Y, Ikeda MA
  • Organizer: Society for Neuroscience 2014 Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Mesenchymal Stem Cells and Bone Tissue Engineering - Overview and Our Approach – (2014)
  • Author(s): Ikeda, MA
  • Organizer: Regional Oral Biology Scientific Meeting 2014
  • Place of Presentation: Depok, Indonesia
  • Year and Date: 2014-10-30 – 2014-10-31
  • Invited
• [Presentation] アポトーシス関連p53標的遺伝子の発現と細胞死誘導におけるDNA結合因子ARID3Bの重要な役割 (2014)
  • Author(s): Endrawan Pratama、井関祥子、池田正明
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Alpha-L-fucosidase (FUCA1) is a p53 target gene, and is expressed at low levels in anaplastic thyroid carcinomas (2013)
  • Author(s): Tsuchida N, Ikeda MA, Kanazawa S, Ishino Y, Kaji K, Salvatore, G, Santoro M, Vecchio G
  • Organizer: 18th World Congress on Advances in Oncology and 16th International Symposium on Molecular Medicine
  • Place of Presentation: Crete, Greece
• [Presentation] ARID3B silencing inhibits E2F-mediated transcription and cell proliferation. (2013)
  • Author(s): Saadat KASM, Ma T, Lestari W, Pratama E, Ohtani K，Ikeda MA
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市、兵庫県
• [Presentation] Association of caspase-8 and p53/p73 deficiencies with chemoresistance in oral carcinoma cells (2013)
  • Author(s): Ikeda, MA
  • Organizer: The 16th Scientific and Refresher Course in Dentistry (KPPIKG 2013)
  • Place of Presentation: Jakarta, Indonesia
  • Invited
• [Presentation] ARID3A and ARID3B play critical roles in Cell Growth and E2F-target gene expression (2012)
  • Author(s): Khandakar A S M Saadat，Widy Lestari, Teng Ma, Endrawan Pratama，Ikuo Morita, Sachiko Iseki, Kiyoshi Ohtani，Masa-Aki Ikeda
  • Organizer: EMBO Young Scientist’s Forum, 2012
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Effects of p53-reactivating compounds Nutlin-3 and RITA on p53 resistance in tumor cells deficient for p53Ser46 phosphorylation (2012)
  • Author(s): 池田 正明
  • Organizer: 第54回歯科基礎医学会学術大会
  • Place of Presentation: 郡山
• [Presentation] Roles of caspase-8 and p53/p73 deficiencies in mitochondria-dependent and drug-induced apoptosis in head and neck carcinoma cells (2012)
  • Author(s): Ikeda MA, Liu J, Uematsu H, Tsuchida N
  • Organizer: 17th World Congress on Advances in Oncology and 15th International Symposium on Molecular Medicine
  • Place of Presentation: Crete, Greece
  • Invited