Feasibility study of RANKL subcellular trafficking as a novel therapeutic target for osteoporosis

• Project/Area Number: 20790129
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: HONMA Masashi The University of Tokyo, 医学部附属病院, 助教 (60401072)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 薬理学 / 生理学 / シグナル伝達 / 発現制御 / 生体分子 / 骨粗鬆症 / 骨芽細胞 / RANKL / トラフィッキング / リソソーム / Vps33a / Class C Vps complex / 分泌 / ClassC Vps complex

Research Abstract

We have found that OPG, which is previously recognized as a decoy receptor for RANKL, forms a complex with RANKL at the Golgi apparatus and the complex formation is necessary for Vps33a-mediated RANKL sorting to the lysosomes in osteoblastic cells. We have also found that RANKL localized at the lysosomes relocate to the cell surface in response to RANK stimulation. These processes can be novel therapeutic targets for osteoporosis.

Research Products

• [Journal Article] (*corresponding) Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis. (2010)
  • Author(s): Shigeki Aoki, Masashi Honma*, Yoshiaki Kariya, Yuko Nakamichi, Tadashi Ninomiya, Naoyuki Takahashi, Nobuyuki Udagawa, Hiroshi Suzuki
  • Journal Title: Journal of Bone and Mineral Research (in press)
• [Journal Article] Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis (2010)
  • Author(s): Shigeki Aoki, Masashi Honma, Yoshiaki Kariya, Yuko Nakamichi, Tadashi Ninomiya, Naoyuki Takahashi, Nobuyuki Udagawa, Hiroshi Suzuki
  • Journal Title: Journal of Bone and Mineral Research (in press)
  • Peer Reviewed
• [Journal Article] (*corresponding) Vps33a Mediates RANKL Storage in Secretory Lysosomes in Osteoblastic Cells. (2009)
  • Author(s): Yoshiaki Kariya, Masashi Honma*, Shigeki Aoki, Atsushi Chiba, Hiroshi Suzuki
  • Journal Title: Journal of Bone and Mineral Research Vol.24Issue10 Pages: 1741-52
• [Journal Article] Vps33a mediates RANKL storage in secretory lysosomes in osteoblastic cells (2009)
  • Author(s): Yoshiaki Kariya, Masashi Honma, Shigeki Aoki, Atsushi Chiba, Hiroshi Suzuki
  • Journal Title: Journal of Bone and Mineral Research Volume 24 Issue 10 Pages: 1741-1752
  • Peer Reviewed
• [Presentation] OPGの生理作用発現における、RANKL細胞内挙動制御の重要性 (2010)
  • Author(s): 青木重樹、本間雅、苅谷嘉顕、鈴木洋史
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis (2009)
  • Author(s): 青木重樹, 本間雅, 苅谷嘉顕, 鈴木洋
  • Organizer: 第32回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] OPGはRANKLの骨芽細胞内選別輸送を担う (2009)
  • Author(s): 青木重樹, 本間雅, 苅谷嘉顕, 鈴木洋史
  • Organizer: 第82回 日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] RANKL storage in secretory lysosomes in osteoblastic cells - the involvement of Vps3 (2009)
  • Author(s): Masashi Honma, Yoshiaki Kariya and Hiroshi Suzuki
  • Organizer: International Bone & Mineral Society and Australian & New Zealand Bone & Mineral Society 2nd Joint Meeting
  • Place of Presentation: Sydney
  • Year and Date: 2009-03-23
• [Presentation] Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis (2009)
  • Author(s): 青木重樹、本間雅、苅谷嘉顕、鈴木洋史
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] OPG functions as a traffic regulator for RANKL. (2009)
  • Author(s): Masashi Honma, Shigeki Aoki, Yoshiaki Kariya, Hiroshi Suzuki
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪
• [Presentation] OPGはRANKLの骨芽細胞内選別輸送を担う (2009)
  • Author(s): 青木重樹、本間雅、苅谷嘉顕、鈴木洋史
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] RANKL storage in secretory lysosomes in osteoblastic cells - the involvement of Vps33a (2009)
  • Author(s): Masashi Honma, Yoshiaki Kariya, Hiroshi Suzuki
  • Organizer: 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society Sydney
• [Presentation] RANKL secretion from secretory lysosomes in osteoblastic cells - the involvement of small GTPase (2009)
  • Author(s): Yoshiaki Kariya, Masashi Honma, Hiroshi Suzuki
  • Organizer: Rab27a/b 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society Sydney
• [Presentation] RANKL secretion from secretory lysosomes in osteoblastic cells - the involvement of Rab27a/b (2008)
  • Author(s): Yoshiaki Kariya, Masashi Honma and Hiroshi Suzuki
  • Organizer: International Bone & Mineral Society and Australian & New Zealand Bone & Mineral Society 2nd Joint Meeting
  • Place of Presentation: Sydney
  • Year and Date: 2008-03-23
• [Presentation] 骨芽細胞におけるRANKL細胞内動態を制御する因子の解析 (2008)
  • Author(s): 本間雅、苅谷嘉顕、青木重樹、鈴木洋史
  • Organizer: 第30回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 札幌