Elucidation of the novel inhibitory mechanism of anti-tumor drug arctigenin on bone resorption

• Project/Area Number: 21592378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: YAMASHITA Teruhito 松本歯科大学, 総合歯科医学研究所, 講師 (90302893)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Naoyuki 松本歯科大学, 総合歯科医学研究所, 教授 (90119222) ; NINOMIYA Tadashi 松本歯科大学, 総合歯科医学研究所, 講師 (00360222)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 破骨細胞 / 骨吸収 / 天然有機化合物 / 抗癌剤 / 抗がん剤

Research Abstract

Arctigenin, an anti-tumor compound, is a plant-derived natural molecule. We find that arctigenin inhibits osteoclast formation and function. In RANKL-induced osteoclastogenesis arctigenin markedly represses the transcriptional activity of NFATc1.Our results suggest that a novel mechanism of NFATc1 in its transcriptional regulation, that is different from a known inhibitory mechanism by which NFATc1 is retained in the cytosol.

Research Products

• [Journal Article] Polarized osteoclasts put marks of tartate-resistant acid phosphatase on dentine slices-a simple method for identifying polarized osteoclasts (2012)
  • Author(s): Nakayama T, et al
  • Journal Title: Bone Volume: 49 Issue: 6 Pages: 1331-1339
  • DOI: 10.1016/j.bone.2011.09.045
  • Peer Reviewed
• [Journal Article] Identification of osteoclasts in culture (2011)
  • Author(s): Udagawa N, et al
  • Journal Title: Methods Mol Biol Volume: 690 Pages: 273-284
  • DOI: 10.1007/978-1-60761-962-8_18
  • ISBN: 9781607619611, 9781607619628
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice (2010)
  • Author(s): Lee JW, et al.
  • Journal Title: Biochem Pharmacol Volume: 80 Pages: 352-361
  • Peer Reviewed
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo (2010)
  • Author(s): Takahashi N, et al.
  • Journal Title: Adv Exp Med Biol Volume: 658 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Diphenylhydantoin inhibits osteoclast differentiation and function through suppression of NFATc1 signaling (2009)
  • Author(s): Koide M, Kinugawa S, Ninomiya T, Mizoguchi T, Yamashita T, Maeda K, Yasuda H, Kobayashi Y, Nakamura H, Takahashi N, Udagawa N
  • Journal Title: Journal of Bone and Mineral Research Volume: 24(8) Issue: 8 Pages: 1469-1480
  • DOI: 10.1359/jbmr.090302
  • Peer Reviewed
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. (2009)
  • Author(s): Mizoguchi T, Muto A, Udagawa N, Arai A, Yamashita T, Hosoya A, Ninomiya T, Nakamura H, Yamamoto Y, Kinugawa S, Nakamura M, Nakamichi Y, Kobayashi Y, Nagasawa S, Oda K, Tanaka H, Tagaya M, Penninger JM, Ito M, Takahashi N.
  • Journal Title: J Cell Biol Volume: 184(4) Issue: 4 Pages: 541-54
  • DOI: 10.1083/jcb.200806139
  • Peer Reviewed
• [Journal Article] Diphenylhydantoin inhibits osteoclast differentiation and function through suppression of NFATc1 signaling (2009)
  • Author(s): Koide M, et al.
  • Journal Title: J Bone Miner Res 24 Pages: 1469-1480
  • Peer Reviewed
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo (2009)
  • Author(s): Mizoguchi T, et al.
  • Journal Title: J Cell Biol 184 Pages: 541-554
  • Peer Reviewed
• [Journal Article] Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners (2009)
  • Author(s): Takahashi M, et al.
  • Journal Title: J Bone Miner Metab 27 Pages: 24-35
  • NAID: 10025336084
  • Peer Reviewed
• [Presentation] アルクチゲニンはNFATc1の核移行を促進するが転写活性を抑制する (2011)
  • Author(s): 山下照仁
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2011-07-30
• [Presentation] 破骨細胞の極性化指標TRAP-markは分泌痕跡である (2011)
  • Author(s): 中山貴裕
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2011-07-28
• [Presentation] 漢方牛蒡子由来のアルクチゲニンは破骨細胞の分化と機能を抑制する (2010)
  • Author(s): 山下照仁
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2010-07-21
• [Book] Identification of osteoclasts in culture. In Embryonic Stem Cell Therapy for Osteo-Degenerative Diseases Series Methods in Molecular Biology (2011)
  • Author(s): Udagawa N, Yamashita T, Kobayashi Y, Takahashi N, Walker JM, zur Nieden NI
  • Publisher: Humana Press
• [Remarks] 松本歯科大学総合歯科医学研究所ホームページ
  • URL: http://www.mdu.ac.jp/laboratory/top_05/index.html