Drug development using a novel immune network analysis method for osteoarthritis

• Project/Area Number: 17K19707
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Onodera Tomohiro 北海道大学, 大学病院, 講師 (70547174)
• Co-Investigator(Kenkyū-buntansha): テルカウィ アラー 北海道大学, 医学研究院, 助教 (00723074)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 関節病学 / 変形性関節症 / ダメージ関連分子パターン / マクロファージ / 慢性炎症 / 免疫学

Outline of Final Research Achievements

A co-culture model system, including cartilage fragments, macrophages, chondrocytes and synovial cells, to simulate the osteoarthritis joint was established. Regarding cartilage fragments, we successfully created cartilage fragments similar in size to that seen in human osteoarthritis. When we observed the cell dynamics of chondrocytes and synovial cells in our original model, we could observe statistically significant changes in the expression of 153 genes. Currently, among these candidate genes, we are conducting functional analysis on the final candidate gene, which is thought to be particularly related to osteoarthritis.

Academic Significance and Societal Importance of the Research Achievements

免疫細胞と軟骨細胞の相互作用を細胞レベルで研究することが可能となるあらたな実験モデルを開発した。また、本プロジェクトで独自に開発したモデルを利用することで、軟骨変性のメカニズムに関する新たな洞察が得られた。本モデルを用いて我々が同定した153種類の遺伝子群には、変形性関節症を制御している因子が含まれている可能性が極めて高く、今後得られた遺伝子群の解析を進めることによって、新たな変形性関節症治療法の開発が可能となる。

Research Products

• [Journal Article] A Novel Cartilage Fragments Stimulation Model Revealed that Macrophage Inflammatory Response Causes an Upregulation of Catabolic Factors of Chondrocytes In Vitro (2019)
  • Author(s): Hamasaki Masanari、Terkawi Mohamad Alaa、Onodera Tomohiro、Homan Kentaro、Iwasaki Norimasa
  • Journal Title: CARTILAGE Volume: In press Issue: 3 Pages: 354-361
  • DOI: 10.1177/1947603519828426
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Blockade of macrophage surface receptors suppresses inflammatory response triggered by cartilage fragments in vitro (2020)
  • Author(s): Masanari Hamsasaki, Mohamad Alaa Terkawi, Tomohiro Onodera, Gen Matsumae, Yuan Tian, Hend Alhasan, Taku Ebata, Norimasa Iwasaki
  • Organizer: The 66th Annual Meeting of the Orthopaedic Research Society, Phoenix Convention Center（Phoenix, Arizona, USA）
• [Presentation] Inflamed macrophages by articular cartilage fragments elicits typical gene expression signature of endochondral ossification in chondrocytes in vitro. (2019)
  • Author(s): Ebata T, Hamasaki M, Terkawi MA, Onodera T, Matsumae G, Tian Y, Alhasan H, Takahashi D, Iwasaki N
  • Organizer: The 66th Annual Meeting of the Orthopaedic Research Society, Phoenix Convention Center（Phoenix, Arizona, USA）
• [Presentation] 軟骨破片刺激モデルにおいて軟骨細胞は軟骨内骨化関連の遺伝子発現が上昇する (2019)
  • Author(s): 江畑拓、濱崎雅成、テルカウイアラー、小野寺智洋、松前元、田園、アルハサンヘンド、宮崎拓自、徐亮、菱村亮介、岩崎倫政
  • Organizer: 第34回 日本整形外科基礎学術集会
• [Presentation] 軟骨破片に対するマクロファージ炎症反応の網羅的遺伝子発現解析 (2019)
  • Author(s): 濱崎 雅成 Mohamad Alaa Terkawi 小野寺 智洋 宝満 健太郎 徐 亮 宮崎 拓自 田 園 江畑 拓 松前 元 岩崎 倫政
  • Organizer: 第34回 日本整形外科基礎学術集会
• [Presentation] Transcriptional profiling of murine macrophages stimulated with cartilage fragments a reveals novel mechanism for osteoarthritis (2019)
  • Author(s): Masanari Hamasaki, Mohamad Alaa Terkawi, Tomohiro Onodera Kentaro Homan, Zenta Joutoku S. Matsubara R. Hishimura, Kim Woo Young, Liang Xu, Norimasa Iwasaki
  • Organizer: International Cartilage Repair Society world congress
• [Presentation] マクロファージ共培養モデルにおいて軟骨破片が引き起こすマクロファージの 炎症反応および軟骨細胞への影響 (2018)
  • Author(s): 濱崎雅成, TERKAWI Mohamad Alaa, 小野寺智洋ら
  • Organizer: 第33回日本整形外科学会基礎学術集会
• [Presentation] マクロファージ共培養モデルにおいて軟骨破片が軟骨細胞に与える影響 (2018)
  • Author(s): 濱崎雅成, TERKAWI Mohamad Alaa, 小野寺智洋ら
  • Organizer: 第31回 日本軟骨代謝学会
• [Presentation] A novel cartilage-fragments stimulation model revealed that macrophage inflammatory response causes an upregulation of catabolic factors of chondrocytes in vitro (2018)
  • Author(s): Masanari Hamasaki, Alaa Terkawi, Tomohiro Onodera et al.
  • Organizer: 2018 Orthopaedic Research Society Annual Meeting
  • Int'l Joint Research
• [Presentation] An Up-Regulation Of Catabolic Factors Of Chondrocytes In Cartilage-Fragments Stimulation Model With Macrophages (2018)
  • Author(s): Masanari Hamasaki, Alaa Terkawi, Tomohiro Onodera et al.
  • Organizer: 2018 International Cartilage Repair Society World Congress
  • Int'l Joint Research
• [Book] 別冊BIO Clinica（バイオクリニカ）慢性炎症と疾患 (2018)
  • Author(s): 小野寺智洋、濱崎雅成、Alaa Terkawi, 岩崎倫政
  • Total Pages: 5
  • Publisher: 北隆館