Analysis of zonal lineage of articular chondrocyte for cartilage regeneration

• Project/Area Number: 15K15546
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: University of Toyama
• Principal Investigator: KIMURA Tomoatsu 富山大学, 大学院医学薬学研究部(医学), 教授 (80167379)
• Co-Investigator(Kenkyū-buntansha): 関 庄二 富山大学, 大学院医学薬学研究部(医学), 助教 (00432112) ; 野上 真紀子 富山大学, 附属病院, 助教 (30750202)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 関節病学 / 軟骨細胞 / 軟骨変性 / 変形性関節症 / 起源 / 分化 / 再生 / 関節軟骨

Outline of Final Research Achievements

We have produced mouse lines with genetic labelling of chondrocyte in surface-deeper zones. After induction of cartilage degeneration by DMM method, YFP+ cells of mid-deep cartilage zone origin appeared as col10+ hypertrophic chondrocytes in the deep zone and calcified zones, indicating these hypertrophic cells were originated from mid-deep zone chondrocytes.
We then, produced sik3 conditional KO mouse in cartilage. After induction of degeneration by DMM, the mouse did not show apparent hypertrophic chondrocyte formation neither in deep zone or calcified zone, suggesting that the inhibition of the sik3 pathway may become a therapeutic target to prevent cartilage degeneration.

Research Products

• [Journal Article] Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3. (2016)
  • Author(s): Yahara Y, Takemori H, Okada M, Kosai A, Yamashita A, Kobayashi T, Fujita K, Itoh Y, Nakamura M, Fuchino H, Kawahara N, Fukui N, Watanabe A, Kimura T, Tsumaki N.
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 10959-10959
  • DOI: 10.1038/ncomms10959
  • NAID: 120005741112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A human amnion-derived extracellular matrix-coated cell-free scaffold for cartilage repair: in vitro and in vivo studies. (2016)
  • Author(s): Nogami M, Kimura T, et al.
  • Journal Title: Tissue Engineering Volume: 22 Issue: 7-8 Pages: 680-688
  • DOI: 10.1089/ten.tea.2015.0285
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 軟骨細胞特異的なSik3の欠失は関節軟骨の厚みを増大させる (2016)
  • Author(s): 箭原 康人, 竹森 洋, 岡田 稔, 高才 東, 山下 晃弘, 小林 与人, 藤田 香里, 伊東 裕美, 中村 正裕, 渕野 裕之, 川原 信夫, 福井 尚志, 渡辺 亮, 木村 友厚, 妻木 範行
  • 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] 骨代謝と軟骨代謝の接点. SIK3をターゲットとした変形性関節症の治療 (2016)
  • Author(s): 箭原 康人, 竹森 洋, 岡田 稔, 高才 東, 山下 晃弘, 小林 与人, 藤田 香里, 伊東 裕美, 中村 正裕, 渕野 裕之, 川原 信夫, 福井 尚志, 渡辺 亮, 木村 友厚, 妻木 範行
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
• [Presentation] SIK経路阻害剤は変形性関節症の進行を抑制する (2016)
  • Author(s): 箭原康人、竹森洋、木村友厚、妻木範行
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広島
  • Year and Date: 2016-02-19