Function of stress effector molecules in the catabolic reactions of chondrocytes and roles in OA progression/repression.

• Project/Area Number: 25462388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kinki University
• Principal Investigator: FUKUDA Kanji 近畿大学, 医学部, 教授 (50201744)
• Co-Investigator(Kenkyū-buntansha): TERAMURA Takeshi 近畿大学, 医学部附属病院, 助教 (40460901)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 変形性関節症 / 活性酸素 / Rhoキナーゼ / TAK1 / 軟骨細胞 / Rho/ROCK / ストレス / Nrf2 / 軟骨 / ストレス応答

Outline of Final Research Achievements

Despite advances in diagnosis, surgery and epidemiological understandings, any effective treatment to prevent or/and cure from osteoarthritis (OA) have not been discovered. Here we searched the effector molecules potentially playing a central role in the stress transduction that can activate OA changes, and found that small-GTPase Rho and Rac had an opposite effect in the cartilage matrix maintenance. We also found that the activity of TGFb-activated kinase 1(TAK1) could be regulated by Rho/ROCK, and the TAK1 activity induced expression of a tissue degeneration factor Cox-2 in the synovial fibroblast cells. Finally, we examined a defensive role of anti-stress molecule Nrf2 against the stress-mediated OA change and demonstrated that Nrf2 was important to maintain chondrocyte matrix. Our findings provide the basis for new biologic and pharmacological approaches to the prevention and treatment of OA.

Research Products

• [Journal Article] Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells. (2015)
  • Author(s): Onodera Y, Teramura T, Takehara T, Shigi K, Fukuda K.
  • Journal Title: FEBS OPEN Bio. Volume: 5 Issue: 1 Pages: 492-501
  • DOI: 10.1016/j.fob.2015.06.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes. (2015)
  • Author(s): Onodera Y, Teramura T, Takehara T, Fukuda K.
  • Journal Title: FEBS OPEN Bio. Volume: 5 Issue: 1 Pages: 476-484
  • DOI: 10.1016/j.fob.2015.05.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant