IL-1 and TLR signals play an important role in mechanical stress-induced osteoarthritis

• Project/Area Number: 15K10492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: NIKI Yasuo 慶應義塾大学, 医学部(信濃町), 准教授 (10276298)
• Co-Investigator(Kenkyū-buntansha): 福原 悠介 慶應義塾大学, 医学部(信濃町), 助教 (60594645) ; 宇田川 和彦 慶應義塾大学, 医学部(信濃町), 助教 (70528364)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: メカニカルストレス / 三次元軟骨モデル / IL-1 / TRPV4 / TLR

Outline of Final Research Achievements

We made a three-dimensional cartilage construct. ATDC5 cells were cultured in alginate beads and seeded within collagen scaffold. Cyclic compressive loading was applied to the cartilage constructs using a cyclic load bioreactor. The mRNA levels of ADAMTS4 and IL-1R1 were substantially increased by the excessive compressive stress. Compressive stress plus subtle level of IL-1β upregulated ADAMTS4 and IL-1R1 expressions. TRPV4 regulated ADAMTS4 and IL-1R1 mRNA levels by cyclic compressive stress. The expression of the IL-1R1 on the surface of chondrocytes would be stimulated by compressive mechanical stress, and subsequent increment of IL-1 susceptibility would be implicated in the OA pathology. TRPV4 channel regulation is one of the most important mechanosensor that controls IL-1 susceptibility and prevents development of OA.

Research Products

• [Presentation] Excessive Cyclic Compression Stress Increases Susceptibility to IL-1 in 3D-cultured Chondrocytes (2018)
  • Author(s): Yuki Takeda, Yasuo Niki, Yusuke Fukuhara, Yoshitsugu Fukuda, Kazuhiko Udagawa, Toshiyuki Kikuchi, Takeshi Miyamoto, Morio Matsumoto, Masaya Nakamura
  • Organizer: 2018 Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] Excessive Cyclic Compression Stress Increases Susceptibility to IL-1 in 3D-cultured Chondrocytes (2017)
  • Author(s): Yuki Takeda, Yasuo Niki, Yusuke Fukuhara, Yoshitsugu Fukuda, Kazuhiko Udagawa, Toshiyuki Kikuchi, Takeshi Miyamoto, Morio Matsumoto, Masaya Nakamura
  • Organizer: 2017 American college of Rheumatology
  • Int'l Joint Research
• [Presentation] ATDC5を用いた三次元培養軟骨モデルの確立とメカニカルストレスの応答性 (2016)
  • Author(s): 武田勇樹 二木康夫 福原悠介 福田良嗣 宇田川和彦 菊地寿幸 宮本健史 松本守雄 中村雅也
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広仁会館（広島県広島市）
  • Year and Date: 2016-02-19
• [Presentation] ATDC5を用いたコラーゲンスポンジ三次元培養軟骨モデルとメカニカルストレスの影響 (2015)
  • Author(s): 武田勇樹 二木康夫 福原悠介 福田良嗣 宇田川和彦 菊地寿幸 宮本健史 松本守雄 中村雅也
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2015-10-22