Development of new OA therapy targeting HIF-1a

• Project/Area Number: 15K15555
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kubo Toshikazu 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20178031)
• Co-Investigator(Kenkyū-buntansha): 新井 祐志 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449) ; 中川 周士 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30643382)
• Co-Investigator(Renkei-kenkyūsha): Mazda Osam 京都府立医科大学, 医学研究科, 教授 (00271164)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 関節軟骨 / 低酸素 / メカニカルストレス / 軟骨 / 整形外科学 / 骨軟骨代謝学 / HIF-1α

Outline of Final Research Achievements

Articular cartilage is physiologically in a hypoxic condition, and HIF-1α is important for chondrocyte survival, differentiation, and metabolism. We tried to force rats to run on treadmill and evaluate that the production of HIF-1, 2α in articular cartilage were changed by running speed. Furthermore, by analyzing the mechanical stress application mechanism in hypoxic condition in vitro, We expected that genes different from regulating in normoxic condition may regulate cartilage metabolism in hypoxic condition.

Research Products

• [Journal Article] Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage (2016)
  • Author(s): Ichimaru S. et al.
  • Journal Title: Int J Mol Sci. Volume: 17 Issue: 7 Pages: 1013-1013
  • DOI: 10.3390/ijms17071013
  • Peer Reviewed / Open Access
• [Presentation] The effect of treadmill running on knee articular cartilage in rats (2017)
  • Author(s): Seiji Shimomura, Hiroaki Inoue, Yuji Arai, Shuji Nakagawa, Shinji Tsuchida, Shohei Ichimaru, Osam Mazda, Toshikazu Kubo
  • Organizer: 20th World Congress of the Osteoarthritis Research Society International (OARSI)
  • Int'l Joint Research
• [Presentation] トレッドミル走行がラット膝関節軟骨に与える影響 (2016)
  • Author(s): 下村征史，井上裕章，新井祐志，中川周士，土田真嗣，市丸昌平，松田 修，久保俊一
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
• [Presentation] 低酸素環境下における外因性ヒアルロン酸の薬理効果の変化 (2016)
  • Author(s): 市丸昌平，中川周士，新井祐志，土田真嗣，井上裕章，下村征史，松田 修，久保俊一
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
• [Presentation] Pharmacological effects of exogenous hyaluronan in articular cartilage under hypoxia (2016)
  • Author(s): Ichimaru S, Nakagawa S, Arai Y, Tsuchida S, Inoue H, Shimomura S, Mazda O, Kubo T
  • Organizer: 19th World Congress of the Osteoarthritis Research Society International (OARSI)
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2016-04-01
  • Int'l Joint Research
• [Presentation] Pharmacological effects of exogenous hyaluronic acid in articular cartilage under hypoxia (2016)
  • Author(s): Ichimaru S, Nakagawa S, Arai Y, Tsuchida S, Inoue H, Shimomura S, Mazda O, Kubo T
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広島
  • Year and Date: 2016-02-19
• [Presentation] 低酸素環境下にある軟骨細胞に対する外因性ヒアルロン酸の薬理効果 (2015)
  • Author(s): 市丸昌平，中川周士，新井祐志，土田真嗣，井上裕章，本城邦晃，白井寿治，寺内 竜，松田 修，久保俊一
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山
  • Year and Date: 2015-10-22
• [Presentation] HSP70 induced by HIF-1α regulates anabolic responses in chondrocytes under hypoxic conditions. (2015)
  • Author(s): Honjo K, Arai Y, Tsuchida S, Nakagawa S, Inoue H, Saito M, Ichimaru S, Shimomura S, Inoue A, Terauchi R, Mazda O, Kubo T
  • Organizer: 18th World Congress of the Osteoarthritis Research Society International (OARSI)
  • Place of Presentation: Seattle, U.S.A
  • Year and Date: 2015-04-30
  • Int'l Joint Research