Development of charge based DDS for OA based on the negative charge of aggrecan

• Project/Area Number: 18K19620
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• 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), 特任教授 (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) ; 井上 裕章 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60457968)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 軟骨 / 変形性関節症 / ヒアルロン酸 / 整形外科学 / 骨軟骨代謝学 / カチオン化 / 軟骨代謝

Outline of Final Research Achievements

The effects of positively charged hyaluronan on articular cartilage were analyzed in in vitro and in vivo experiments. The expression of anabolic factors in the positively charged hyaluronan group was not different from that in the conventional hyaluronan group, and cationization did not have a negative effect on cartilage metabolism. In vivo, positively charged hyaluronan tended to be more effective in preventing cartilage degeneration than conventional hyaluronan, suggesting that the effect of positively charged hyaluronan on cartilage may be sustained by long-term adsorption to articular cartilage.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症（osteoarthritis: OA）に対する根本的な治療薬を開発するためには，OAの病態解明による創薬と同時に，未だ困難とされる軟骨細胞へのDDSの開発を並行して行う必要がある．今回のDDSの開発は，標的臓器の特徴に着目することが斬新である．本研究で得られた知見によりcharge based DDSを創製できれば，OAに対する斬新な薬物療法の開発に向けて大きく前進すると考える．さらに，本研究の成功は今後の薬剤開発において組織環境が重要であることを提言し，他分野の新規薬剤開発，修飾でも寄与することが期待される．

Research Products

• [Presentation] 酸素濃度がヒトiPS細胞から軟骨組織への分化に与える影響 (2021)
  • Author(s): 藤井雄太，井上裕章，下村征史，中川周士，市丸昌平，鎌田陽一郎，貝原健太，松田 修，新井祐志
  • Organizer: 第33回日本軟骨代謝学会
• [Presentation] Treadmill running suppressed joint destruction in a rheumatoid arthritis rat model (2020)
  • Author(s): Fujii Y, Inoue H, Arai Y, Shimomura S, Nakagawa S, Tsuchida S, Kamada Y, Kaihara K, Mazda O, Mikami Y
  • Organizer: 66th Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] トレッドミル走行がラット関節炎モデルの足関節に与える影響 (2020)
  • Author(s): 藤井雄太，井上裕章，中川周士，下村征史，新井祐志，松田 修，高橋謙治
  • Organizer: 第35回日本整形外科学会基礎学術集会
• [Presentation] Analysis Of Reaction To Tensile Stress In Chondrocytes In Hypoxic Environment (2020)
  • Author(s): Yoichiro Kamada; Hiroaki Inoue; Yuji Arai; Seiji Shimomura; Shuji Nakagawa; Shinji Tsuchida; Yuta Fujii; Kenta Kaihara; Osam Mazda; Yasuo Mikami
  • Organizer: 2020 Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] The effects of treadmill exercise at a single time on knee articular cartilage in vivo (2018)
  • Author(s): Shimomura S, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Ichimaru S, Fujii Y, Mazda O, Kubo T
  • Organizer: 26th Annual Meeting of European Orthopaedic Reserch Society
  • Int'l Joint Research
• [Presentation] ヒトiPS細胞から軟骨組織分化における酸素濃度の影響の検討 (2018)
  • 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，藤井雄太，松田 修，久保俊一
  • Organizer: 第33回日本整形外科基礎学術集会