Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model

• Project/Area Number: 18K09105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kobe University
• Principal Investigator: Hayashi Shinya 神戸大学, 医学部附属病院, 助教 (20437487)
• Co-Investigator(Kenkyū-buntansha): 松本 知之 神戸大学, 医学部附属病院, 講師 (50546588) ; 橋本 慎吾 神戸大学, 医学研究科, 特命助教 (20457089) ; 高山 孝治 神戸大学, 医学部附属病院, 医学研究員 (80546490)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: EPA / ゼラチンハイドロゲル / エイコサペンタ塩酸 / 抗酸化 / 変形性関節症 / 軟骨 / 炎症

Outline of Final Research Achievements

This study aimed to investigate the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo.Ten-week-old male C57BL/6J mice were randomly divided into six groups (six mice each): sham,destabilization of the medial meniscus (DMM), Corn (DMM + corn oil ), EPA-I (DMM + corn oil + 3 mg/ml EPA), Control (DMM + control gelatin hydrogels), and EPA-G (DMM + 3 mg/ml EPA-incorporating gelatin hydrogels) groups. Mice were then euthanized 8 weeks after DMM or sham surgery, and subjected to histological evaluation. Histologic score was significantly improved in EPA-G compared to in EPA-I. MMP-3-, MMP-13-, IL-1β-, and p-IKK α/β-positive cell ratio was significantly improved in EPA-G compared to in EPA-I. However, CD86- and CD163-positive cell ratio was not significantly different between EPA-I and EPA-G. EPA-incorporating gelatin hydrogels can prevent OA progression in vivo more effectively than single injection of EPA.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症に対する新規治療薬の開発で現在のところ効果的且つ安全性の高い治療法
は無い。EPAは抗酸化剤としての機能だけでなく、近年抗炎症作用も有する報告もあり、多機能を有することが予想されEPAの他疾患への応用も含め機能を解明することが本研究の学術的意義であり、一方でEPAは循環器系やアルツハイマー病などの治療薬としてすでに使用されており、薬としての安全性は担保されているため変形性関節症の治療薬として即戦力になることが期待される点で社会的意義がある。

Research Products

• [Journal Article] Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model (2020)
  • Author(s): Tsubosaka Masanori、Kihara Shinsuke、Hayashi Shinya、Nagata Junpei、Kuwahara Toshie、Fujita Masahiro、Kikuchi Kenichi、Takashima Yoshinori、Kamenaga Tomoyuki、Kuroda Yuichi、Takeuchi Kazuhiro、Fukuda Koji、Takayama Koji、Hashimoto Shingo、Matsumoto Tomoyuki、Niikura Takahiro、Tabata Yasuhiko、Kuroda Ryosuke
  • Journal Title: Journal of Orthopaedic Research Volume: 38 Issue: 10 Pages: 2157-2169
  • DOI: 10.1002/jor.24688
  • Peer Reviewed
• [Presentation] The influence of gelatin hydrogel including eicosapentaenoic acid on the osteoarthritis progression in vivo (2020)
  • Author(s): Tsubosaka M
  • Organizer: Annual Meeting of the Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model. (2020)
  • Author(s): Masanori Tsubosaka
  • Organizer: Orthopaedics Reserch Society (ORS) 2020 annual meeting
• [Presentation] エイコサペンタエン酸含有ゼラチンハイドロゲルは変形性関節症進行を抑制する (2019)
  • Author(s): 壷坂 正憲
  • Organizer: 第34回日本整形外科学会基礎学術集会