The role of Wnt5a in osteoblast and osteosarcoma

• Project/Area Number: 26861181
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Shinshu University
• Principal Investigator: OKAMOTO Masanori 信州大学, 医学部附属病院, 助教(診療) (50596781)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Wntシグナル / Wnt5a / Lrp5/6 / 骨芽細胞分化 / 骨形成 / 骨肉腫 / 骨芽細胞 / Lｒｐ5/6 / 骨代謝

Outline of Final Research Achievements

Wnt ligands regulate bone formation through beta-catenin-dependent canonical and beta-catenin-independent noncanonical Wnt signaling pathways. The two signaling pathways cooperate with each other during osteoblastogenesis, although noncanonical Wnt5a antagonizes the canonical Wnt pathway in various types of cells. This study revealed that Wnt5a-induced noncanonical signals enhance the canonical Wnt pathway through up-regulation of Lrp5/6 to achieve proper bone formation.
We also found that Wnt5a up-regulate Lrp5/6 expression in the human osteosarcoma cell (malignant bone tumor). Furthermore, this study suggested that Wnt5a regulate cell proliferation and migration of osteosarcoma.

Research Products

• [Presentation] 非古典経路のWNT5Aは骨肉腫においてLRP5/6の発現を調節する (2016)
  • Author(s): 岡本正則，吉田和薫，青木 薫，鬼頭宗久，田中厚誌，鈴木周一郎，髙沢 彰，福澤拓馬，薄井雄企，羽二生久夫，小林伸輔，田中学，吉村康夫，小林泰浩，加藤博之，齋藤直人
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Year and Date: 2016-10-13
• [Presentation] Noncanonical WNT5A regulates the expression of LRP5/6 in osteosarcoma (2016)
  • Author(s): Masanori Okamoto, Kazushige Yoshida, Kaoru Aoki, Munehisa Kito, Atsushi Tanaka, Shuichiro Suzuki, Akira Takazawa, Yasuo Yoshimura, Hiroyuki Kato, Naoto Saito
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
  • Place of Presentation: Maui, Hawaii, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Noncanonical Wnt5a enhances Wnt/b-catenin signaling through the up-regulation of Lrp5/6 during osteoblastogenesis (2014)
  • Author(s): Masanori Okamoto, Nobuyuki Udagawa, Teruhito Yamashita, Shunsuke Uehara, Kaoru Aoki, Hisao Haniu, Hiroyuki Kato, Naoto Saito, Naoyuki Takahashi, Yasuhiro Kobayashi
  • Organizer: ANZBMS Annual Scientific Meeting
  • Place of Presentation: MILLENNIUM HOTEL, QUEENSTOWN 9300, NEW ZEALAND
  • Year and Date: 2014-09-07 – 2014-09-10