Osteoclastogenesis from embryonic macrophages: Novel cell fate analysis and regulation of bone metabolism

• Project/Area Number: 26670803
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: Kukita Toshio 九州大学, 歯学研究科(研究院), 教授 (70150464)
• Co-Investigator(Kenkyū-buntansha): KUKITA AKIKO 佐賀大学, 医学部, 准教授 (30153266)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 破骨細胞 / 胎生期マクロファージ / Fate Mapping解析 / アンチセンスRNA / 新生仔破骨細胞 / Fate Mapping 解析 / 骨代謝制御 / Fate Mapping 解析 / 血島

Outline of Final Research Achievements

Purpose of this research is to verify a hypothesis that osteoclasts are derived from macrophages observed in the embryonic stages. As we could not obtain mice required for performing Fate Mapping analysis of the early embryonic macrophages, we have changed research strategy. We have characterized the properties of osteoclasts present in newborn animals, which are supposed to be formed from cells in macrophages-lineage present in embryos. We have focused on investigating an involvement of WT1, zinc-finger transcription factor having the ability to induce macrophage differentiation, in the generation of osteoclasts present in newborn rats. We have detected a marked expression of antisense RNA for WT1(WT1asRNA)in active osteoclasts present in newborn rats. Over-expression of WT1asRNA in osteoclast precursors significantly augmented osteoclastogenesis. These data show that osteoclastogenesis is controlled by WT1asRNA at least in osteoclastogenesis from fetal osteoclast precursors.

Research Products

• [Journal Article] Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells. (2016)
  • Author(s): Sonoda S, Yamaza H, Ma L, Tanaka Y, Tomoda E, Aijima R, Nonaka K, Kukita T, Shi S, Nishimura F, Yamaza T.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 19286-19286
  • DOI: 10.1038/srep19286
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Membrane Nanotube Formation in Osteoclastogenesis. (2015)
  • Author(s): Kukita T., Takahahsi A., Zhang J-Q., Kukita A.
  • Journal Title: Kurt Pfannkuche (ed), Cell Fusion: Overviews and Methods, Methods in Molecular Biology Volume: 1313 Pages: 193-202
  • DOI: 10.1007/978-1-4939-2703-6_14
  • ISBN: 9781493927029, 9781493927036
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody. (2015)
  • Author(s): Mine Y, Shuto T, Nikawa H, Kawai T, Ohara M, Kawahara K, Ohta K, Kukita T, Terada Y, Makihira S.
  • Journal Title: Cell Biol Int. Volume: 39 Issue: 6 Pages: 696-709
  • DOI: 10.1002/cbin.10447
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 炎症性骨破壊の免疫学的制御：病的骨破壊のみを制御する「安全かつ強力な次世代型骨代謝制御法」の開発をめざして (2015)
  • Author(s): 久木田敏夫、久木田明子
  • Journal Title: 臨床免疫・アレルギー科（科学評論社） Volume: 64(2) Pages: 113-120
• [Journal Article] Involvement of deoxyadenosine and adenosine deaminase in the Methotrexate-induced suppression of inflammatory bone destruction. (2015)
  • Author(s): Qu P-F., Kukita A., Li Y-J., Moriyama K., Lei L., Kukita T.
  • Journal Title: In: Adenosine Receptors: Pharmacology, Functions and Therapeutic aspects. Ed. Warrick K., Volume: ISBN: 978-1-63463-454-0 Pages: 143-164
  • Peer Reviewed
• [Journal Article] Involvement of CXCL14 in osteolytic bone metastasis from lung cancer. (2014)
  • Author(s): Takiguchi S, Korenaga N, Inoue K, Sugi E, Kataoka Y, Matsusue K, Futagami K, Li YJ, Kukita T, Teramoto N, Iguchi H.
  • Journal Title: Int J Oncol. Volume: 44（4) Issue: 4 Pages: 1316-1324
  • DOI: 10.3892/ijo.2014.2293
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction. (2014)
  • Author(s): K. Moriyama, A. Kukita, Y-J. Li, N. Uehara, J-Q Zhang, I. Takahashi, T. Kukita
  • Journal Title: Lab. Invest Volume: 94(11) Issue: 11 Pages: 1200-1211
  • DOI: 10.1038/labinvest.2014.107
  • Peer Reviewed / Open Access
• [Journal Article] Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis (2014)
  • Author(s): Takano, T. Li, Y. J. Kukita, A. Yamaza, T. Ayukawa, Y. Moriyama, K. Uehara, N. Nomiyama, H. Koyano, K. and Kukita, T.
  • Journal Title: Laboratory Investigation Volume: 94 Issue: 3 Pages: 286-296
  • DOI: 10.1038/labinvest.2013.152
  • Peer Reviewed / Open Access
• [Presentation] ラミニン322によるRANK発現調節とマクロファージ-破骨細胞分化転換の制御 (2015)
  • Author(s): 上原範久、久木田明子、久本由香里、保田尚孝、久木田敏夫
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
• [Presentation] Galectin-9による破骨細胞分化制御メカニズムの解明：NFATc1の発現を抑制する転写因子MafB及びIRF-8の関与 (2015)
  • Author(s): 久本由香里、上原範久、久木田明子、久木田敏夫
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
• [Presentation] Ndd4ユビキチンリガーゼ結合タンパク質Pmepa1の破骨細胞の分化と機能における新たな役割 (2015)
  • Author(s): 徐祥赫、舟久保立、白木誠、久木田敏夫、久木田明子
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
• [Presentation] 免疫調節膜表面分子Tim-3の破骨細胞での発現と炎症性骨破壊制御 (2014)
  • Author(s): 森山加奈子、久木田明子、上原範久、久本由香里、高橋一郎、久木田敏夫
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] 免疫調節膜表面分子Tim-3を介する炎症性骨破壊制御 (2014)
  • Author(s): 森山加奈子、久木田明子、上原範久、久本由香里、高橋一郎、久木田敏夫
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-24 – 2014-07-26
• [Book] ADENOSINE RECEPTORS Pharmacology, Functions and Therapeutic Aspects: Involvement of Deoxyadenosine and Adenosine Deaminase in the Methotrexate-induced Suppression of Inflammatory Bone Destruction (2015)
  • Author(s): Peng-fei Qu, Akiko Kukita, Yin-ji Li, Kanako Moriyama, Lin Lei, Toshio Kukita
  • Total Pages: 23
  • Publisher: Nova Science Publishers, Inc. New York