Analyses of Notch signaling pathway in osteoarthritis

• Project/Area Number: 24592222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: TAKETOMI Shuji 東京大学, 医学部附属病院, 助教 (70570018)
• Co-Investigator(Kenkyū-buntansha): OGATA Naoshi 帝京大学, 医学部, 教授 (10361495) ; CHIKUDA Hirotaka 東京大学, 医学部附属病院, 准教授 (30345219) ; SAITO Taku 東京大学, 医学部附属病院, 特任准教授 (30456107)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 整形外科学 / 変形性関節症 / 関節軟骨 / Hes1 / Camk2 / Adam17 / Notchシグナル

Outline of Final Research Achievements

Adam10 and Adam17 were abundantly expressed during articular cartilage degeneration of mouse osteoarthritis model. When we suppressed them by their specific siRNA, hypertrophic differentiation of chondrocytes was inhibited. As downstream signal, we showed that Hes1 promoted cartilage degeneration by inducing Adamts5 and Mmp13. We further performed microarray analysis and identified IL6 and IL1RL1 as its direct target.

Research Products

• [Journal Article] Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2. (2015)
  • Author(s): Sugita S, Taketomi S, Saito T, et al.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112 Issue: 10 Pages: 3080-5
  • DOI: 10.1073/pnas.1419699112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis (2014)
  • Author(s): Okada K, Saito T, et al.
  • Journal Title: PLoS One. Volume: 9 Issue: 12 Pages: e115169-e115169
  • DOI: 10.1371/journal.pone.0115169
  • Peer Reviewed / Open Access
• [Journal Article] Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model. (2014)
  • Author(s): Yano F, Saito T, et al.
  • Journal Title: Ann Rheum Dis. Volume: 73 Issue: 11 Pages: 2062-4
  • DOI: 10.1136/annrheumdis-2014-205672
  • Peer Reviewed
• [Journal Article] Remnant-preserving anterior cruciate ligament reconstruction using a three-dimensional fluoroscopic navigation system (2014)
  • Author(s): Taketomi S, et al.
  • Journal Title: Knee Surg Relat Res. Volume: 26 Issue: 3 Pages: 168
  • DOI: 10.5792/ksrr.2014.26.3.168
  • Peer Reviewed
• [Journal Article] Clinical features and injury patterns of medial collateral ligament tibial side avulsions: "Wave sign" on magnetic resonance imaging is essential for diagnosis (2014)
  • Author(s): Taketomi S, et al.
  • Journal Title: Knee Volume: 21 Issue: 6 Pages: 1151
  • DOI: 10.1016/j.knee.2014.08.019
  • Peer Reviewed
• [Presentation] Transcription factor hes1 modulates osteoarthritis development in cooperation with CaMKII. (2014)
  • Author(s): Sugita S, Saito T, et al.
  • Organizer: Annual meeting of Osteoarthritis Research Society International.
  • Place of Presentation: Paris
  • Year and Date: 2014-04-25
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/