Establishment of a research platform for developing radical treatment and early predictive diagnostics for scoliosis through nutritional environmental signals

• Project/Area Number: 17KT0051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Gifu Pharmaceutical University (2019); Kanazawa University (2017-2018)
• Principal Investigator: Eiichi Hinoi 岐阜薬科大学, 薬学部, 教授 (70360865)
• Co-Investigator(Kenkyū-buntansha): 小林 功 金沢大学, 生命理工学系, 助教 (30774757)
• Project Period (FY): 2017-07-18 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 脊椎側弯症 / アミノ酸

Outline of Final Research Achievements

The present study aimed to investigate the importance of amino acid signal for onset and progression of scoliosis with rib anomalies using genetically modified mice. Serious scoliosis with thoracic deformity was caused by inactivation of amino acid transporter and activation of mTOR signaling in chondrocyte. These results suggest that dysfunction of amino acid signal may be involved in the onset and progression of scoliosis.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、軟骨細胞のアミノ酸トランスポーター/mTORC1シグナルは、脊椎恒常性維持に重要な役割を果たしており、その機能破綻により脊椎側弯症が生じる可能性が示唆された。これらの成果を基盤として、アミノ酸トランスポーターを分子基軸とした思春期突発性脊椎側弯症に対する根本治療薬開発および早期予測診断技術開発を行うための研究基盤が確立されることが期待される。

Research Products

• [Int'l Joint Research] Columbia University(米国)
• [Journal Article] mTORC1 Activation in Osteoclasts Prevents Bone Loss in a Mouse Model of Osteoporosis. (2019)
  • Author(s): Hiraiwa M, Ozaki K, Yamada T, Iezaki T, Park G, Fukasawa K, Horie T, Kamada H, Tokumura K, Motono M, Kaneda K, Hinoi E.
  • Journal Title: Front Pharmacol. Volume: 10 Pages: 00684-00684
  • DOI: 10.3389/fphar.2019.00684
  • Peer Reviewed / Open Access
• [Journal Article] The L-type amino acid transporter LAT1 inhibits osteoclastogenesis and maintains bone homeostasis through the mTORC1 pathway (2019)
  • Author(s): Ozaki Kakeru、Yamada Takanori、Horie Tetsuhiro、Ishizaki Atsushi、Hiraiwa Manami、Iezaki Takashi、Park Gyujin、Fukasawa Kazuya、Kamada Hikari、Tokumura Kazuya、Motono Mei、Kaneda Katsuyuki、Ogawa Kazuma、Ochi Hiroki、Sato Shingo、Kobayashi Yasuhiro、Shi Yun-Bo、Taylor Peter M.、Hinoi Eiichi
  • Journal Title: Science Signaling Volume: 12 Issue: 589 Pages: 589-589
  • DOI: 10.1126/scisignal.aaw3921
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis. (2018)
  • Author(s): Iezaki T, Fukasawa K, Horie T, Park G, Robinson S, Nakaya M, Fujita H, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Yoneda Y, Takarada T, Guo XE, Kurose H, Hinoi E.
  • Journal Title: Development Volume: 145 Issue: 14 Pages: 164004-164004
  • DOI: 10.1242/dev.164004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis. (2018)
  • Author(s): Iezaki T, Horie T, Fukasawa K, Kitabatake M, Nakamura Y, Park G, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Manabe T, Ishigaki Y, Ohno M, Hinoi E.
  • Journal Title: Stem Cell Reports Volume: 11 Issue: 1 Pages: 228-241
  • DOI: 10.1016/j.stemcr.2018.05.020
  • Peer Reviewed / Open Access
• [Presentation] アミノ酸トランスポーターと骨代謝 (2019)
  • Author(s): 檜井栄一
  • Organizer: 第14回トランスポーター研究会年会
  • Invited
• [Presentation] 骨を造る細胞の新たな役割 ～免疫・代謝・記憶～ (2018)
  • Author(s): 檜井栄一
  • Organizer: 第40回日本臨床栄養学会総会・第39回日本臨床栄養協会総会・第16回大連合大会
  • Invited
• [Presentation] 骨軟骨代謝調節と時計遺伝子について (2018)
  • Author(s): 檜井栄一
  • Organizer: 第25回日本時間生物学会学術大会
  • Invited