Distinguishing the Proapoptotic and Antiresorptive Functions of Bisphosphonates inMurine Osteoclasts

• Project/Area Number: 22591679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: OHSHIMA Yasushi 東京大学, 医学部附属病院, 助教 (50570016)
• Co-Investigator(Kenkyū-buntansha): TANAKA Sakae 東京大学, 医学部附属病院, 教授 (50282661) ; TAKETOMI Shuji 東京大学, 医学部附属病院, 助教 (70570018) ; 小倉 浩一 東京大学, 医学部附属病院, 助教 (20583115) ; 増出 和浩 (増田 和浩) 東京大学, 医学部附属病院, 助教 (70407948)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨 / 軟骨代謝学 / 骨・軟骨代謝学 / リセドロネート / 破骨細胞 / 細胞骨格 / Akt

Research Abstract

Nitrogen-containing bisphosphonates are one of the most successful therapeutics for osteoporosis. The aim of this study was to elucidate the functional mechanism of nitrogencontaining bisphosphonates. This study indicates that the antiresorptive effect of nitrogen-containing bisphosphonates is mainly mediated by the suppression of the bone-resorbing activity of osteoclasts and not by the induction of osteoclast apoptosis.

Research Products

• [Journal Article] Distinguishing the proapoptotic and antiresorptive functions of risedronate in murine osteoclasts: role of the Akt pathway and the ERK/Bim axis. (2011)
  • Author(s): Matsumoto T, Nagase Y, Iwasawa M, Yasui T, Masuda H, Kadono Y, Nakamura K, Tanaka S.
  • Journal Title: Arthritis and Rheumatism. Volume: Vol.63
• [Journal Article] Distinguishing the proapoptotic and antiresorptive functions of risedronate in murine osteoclasts: Role of the akt pathway and the ERK/Bim axis (2011)
  • Author(s): Matsumoto T, Nagase Y, Iwasawa M, Yasui T, Masuda H, Kadono Y, Nakamura K, Tanaka S
  • Journal Title: Arthritis and Rheumatism Volume: 63 Issue: 12 Pages: 3908
  • DOI: 10.1002/art.30646
  • Peer Reviewed
• [Journal Article] Antiapoptotic molecule Bcl-2 is essential for the anabolic activity of parathyroid hormone in bone. (2010)
  • Author(s): Nagase Y, et al.
  • Journal Title: Ann N Y Acad Sci. Volume: 1192 Pages: 330-337
  • Peer Reviewed
• [Journal Article] Regulation of RANKL-induced osteoclastogenesis by TGF-β through mole cular interaction between Smad3 and Traf6. (2010)
  • Author(s): Yasui T, et al.
  • Journal Title: J Bone Miner Res Volume: (Online publication)
  • Peer Reviewed
• [Presentation] Segregation of pro-apoptotic and anti-resoptive functions of risedronate in vivo (2010)
  • Author(s): Takumi Matsumoto, Yuho KadonoTetsuroYasui, Hironari Masuda, Kozo Nakamura, Stakae Tanaka..
  • Organizer: 32nd Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2010-10-15
• [Presentation] Regulation of Apoptosis and Function of Osteoclasts by Bcl-2 Family Proteins (2010)
  • Author(s): 田中栄
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-27
• [Presentation] リセ ドロネートの in vivo における骨吸収 抑制効果は破骨細胞のアポトーシスに依 存しない (2010)
  • Author(s): 松本卓巳、永瀬雄一、安井哲郎、増田裕也、門野夕峰、中村耕三、田中栄.
  • Organizer: 日本骨代謝学会学術集会(第28回)
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] Erk and Akt pathways are modulated by risedronate and reciprocally regulate apoptosis and activity of osteoclasts: insight into in vivo mechanism of action (2010)
  • Author(s): Takumi Matsumoto, Yuho Kadono, Tetsuro Yasui, Hironari Masuda, Kozo Nakamura, Stakae Tanaka.
  • Organizer: 3rd International Conference on Osteoimmunology
  • Place of Presentation: Fira, Greece
  • Year and Date: 2010-06-20