Molecular mechanisms of nerve-vessel-bone network

• Project/Area Number: 26293432
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Saitama Medical University
• Principal Investigator: SATO Tsuyoshi 埼玉医科大学, 医学部, 准教授 (60406494)
• Co-Investigator(Kenkyū-buntansha): 臼井 通彦 九州歯科大学, 歯学部, 准教授 (10453630) ; 竹田 秀 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30376727) ; 水野 洋介 埼玉医科大学, 医学部, 助教 (30406532) ; 古株 彰一郎 九州歯科大学, 歯学部, 准教授 (30448899) ; 松本 征仁 埼玉医科大学, 医学部, 講師 (90321819)
• Co-Investigator(Renkei-kenkyūsha): OKAZAKI Yasushi 埼玉医科大学, 医学部, 教授 (80280733) ; SUDA Tatsuo 埼玉医科大学, 医学部, 客員教授 (90014034) ; NISHIHARA Tatsuji 九州歯科大学, 歯学部, 教授 (80192251) ; YODA Testuya 埼玉医科大学, 医学部, 教授 (60242210)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: netrin-4 / semaphorin 3A / 骨細胞 / 血管内皮細胞 / 破骨細胞 / 骨・神経・血管 / 骨減少症 / ネットワーク機構 / 骨芽細胞 / 神経芽細胞 / ネットワーク / 分化 / 遺伝子網羅的解析 / 遊走能 / 分化能 / CDK6 / 骨代謝 / 血管系 / 神経系

Outline of Final Research Achievements

Bone is a highly vascularized organ, thus angiogenesis appears a vital process during bone remodeling. However, the role of vascular systems in bone remodeling and the effect of Sema3A on dendritic processes of osteocyte cell line are not well understood.
Here we show that netrin-4 inhibits osteoclast differentiation in vitro and in vivo. Co-cultures of bone marrow macrophages with vascular endothelial cells markedly inhibited osteoclast differentiation. Administration of netrin-4 prevented bone loss in an osteoporosis mouse model by decreasing the osteoclast number. We also found that Sema3A regulates dendrites of osteocytes in association with downregulation of Cdk6.

Research Products

• [Journal Article] Semaphorin 3A Promotes Dendrite Elongation of Osteocytes in Association with Down-regulation of CDK6. (2016)
  • Author(s): Niimura M, Sato T, Enoki Y, Okubo M, Kokabu S, Takeda S, Yoda T.
  • Journal Title: In Vivo Volume: 30 Pages: 231-236
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Netrin-4 derived from murine vascular endothelial cells inhibits osteoclast differentiation in vitro and prevents bone loss in vivo. (2014)
  • Author(s): Matsumoto, Masahiko Okubo, Keisuke Nakashima, Masayuki Yamato, Teruo Okano, Toru Fukuda, Dai Chida, Yuuki Imai, Hisataka Yasuda, Tatsuji Nishihara, Masumi Akita, Hiromi Oda, Yasushi Okazaki, Tatsuo Suda, Tetsuya Yoda
  • Journal Title: FEBS Lett. Volume: 588 Issue: 14 Pages: 2262-2269
  • DOI: 10.1016/j.febslet.2014.05.009
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 骨芽細胞と神経芽細胞は相互に分化を促進させる (2016)
  • Author(s): 塘田健人、佐藤毅、大久保正彦、榎木祐一郎、古株彰一郎、依田哲也
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-04-16
• [Presentation] Netrin4を介した血管内皮細胞による新たな骨代謝調節機構と骨粗鬆症に対する臨床応用 (2014)
  • Author(s): 榎木祐一郎，佐藤毅，林直樹，北村智久，大久保正彦，古株彰一郎，福島洋介，新村昌弘，依田哲也
  • Organizer: 第68回日本口腔科学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-05-07 – 2014-05-09
• [Book] Vascular endothelial cells inhibitosteoclast differentiation via not osteoprotegerin but netrin-4 (2015)
  • Author(s): Enoki Y, Sato T, Yumoto M, Ikami, E, Kitamura T, Hayashi N, Nakanoka C, Okubo M, Sano Y, Fukushima Y, Kokabu S, Yoda T
  • Total Pages: 2
  • Publisher: Japanese Stomatological society