New development of the molecular targeted therapy for osteoarthritis arthritis with respect to stress-response mechanism

• Project/Area Number: 24390356
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kubo Toshikazu 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20178031)
• Co-Investigator(Kenkyū-buntansha): ARAI YUJI 京都府立医科大学, 医学研究科, 講師 (50347449) ; Terauchi Ryu 京都府立医科大学, 医学研究科, 講師 (20575154) ; Fujiwara Hiroyoshi 京都府立医科大学, 医学研究科, 准教授 (90381962)
• Co-Investigator(Renkei-kenkyūsha): Mazda Osam 京都府立医科大学, 医学研究科, 教授 (00271164)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 変形性関節症 / ストレス応答機構 / 関節軟骨 / 軟骨細胞 / メカニカルストレス / 軟骨代謝 / ストレス応答 / HSP70

Outline of Final Research Achievements

We showed that expression of HIF-2α in cultured chondrocytes is induced independent of NF-κB expression under a hydrostatic pressure of 5 MPa. These results may help in elucidation of the pathology of OA because HIF-2α and MMPs, acting downstream of HIF-2α, are involved in initiation and progression of OA. Further, as compared to 10 m/min group and 12m/min group, 20 m/min group exercise was found to be excessive, since OA had progressed in 20 m/min group. We considered that excessive forced running caused the progression of OA.

Research Products

• [Journal Article] Hydrostatic Pressure Influences HIF-2 Alpha Expression in Chondrocytes (2015)
  • Author(s): Hiroaki Inoue, Yuji Arai, Tsunao Kishida, Ryu Terauchi, Kuniaki Honjo, Shuji Nakagawa, Shinji Tsuchida, Tomohiro Matsuki, Keiichirou Ueshima, Hiroyoshi Fujiwara, Osam Mazda, Toshikazu Kubo
  • Journal Title: International Journal of Molecular Sciences Volume: 16 Pages: 1043-1050
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3 MHz pulsed ultrasound (2014)
  • Author(s): Inoue H, Arai Y, Kishida T, Shin-Ya, M, Terauchi R, Nakagawa S, Saito M, Tsuchida, S, Inoue A, Shirai T, Fujiwara H, Mazda O, Kubo T
  • Journal Title: Ultrasonics Volume: 54(3)(Epub 2013 Nov 11) Issue: 3 Pages: 874-81
  • DOI: 10.1016/j.ultras.2013.10.021
  • Peer Reviewed
• [Presentation] Pharmacological effects of exogenous hyaluronic acid in articular cartilage under hypoxia (2016)
  • Author(s): Ichimaru S, Nakagawa S, Arai Y, Tsuchida S, Inoue H, Shimomura S, Mazda O, Kubo T
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広島
  • Year and Date: 2016-02-19
• [Presentation] 低酸素環境下にある軟骨細胞に対する外因性ヒアルロン酸の薬理効果 (2015)
  • Author(s): 市丸昌平，中川周士，新井祐志，土田真嗣，井上裕章，本城邦晃，白井寿治，寺内 竜，松田 修，久保俊一
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山
  • Year and Date: 2015-10-22
• [Presentation] HSP70 induced by HIF-1α regulates anabolic responses in chondrocytes under hypoxic conditions (2015)
  • Author(s): Honjo K, Arai Y, Tsuchida S, Nakagawa S, Inoue H, Saito M, Ichimaru S, Shimomura S, Inoue A, Terauchi R, Mazda O, Kubo T
  • Organizer: 18th World Congress of the Osteoarthritis Research Society International (OARSI)
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] Effect of inflammation stress on the hypertrophic differentiation-related gene expression in cultured chondrocytes (2014)
  • Author(s): Inoue Hiroaki, Arai Yuji, Terauchi Ryu, Nakagawa Shuji, Saito Masazumi, Tsuchida Shinji, Matsuki Tomohiro, Ichimaru Shohei, Mazda Osam,Kubo Toshikazu
  • Organizer: 2015 OARSI World Congress
  • Place of Presentation: Paris, France
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 低酸素環境下の軟骨細胞におけるheat shock protein 70の役割 (2013)
  • Author(s): 土田真嗣,新井祐志,寺内 竜,中川周士,井上敦夫,平岡延之,井上裕章,齊藤正純,松木智宏,久保俊一
  • Organizer: 第26回日本軟骨代謝学会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2013-03-02
• [Presentation] 活性化マクロファージに対するランソプラゾールの抗炎症効果の解析 (2013)
  • Author(s): 中川周士，新井祐志，井上裕章，土田真嗣，小田 良，徳永大作，川人 豊，妹尾高宏，久保俊一
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Effect of mechanical stress on the hypertrophic differentiation related gene expression in cultured chondrocytes (2013)
  • Author(s): Inoue H, Arai Y, Terauchi R, Nakagawa S, Saito M, Hiraoka N, Tsuchida S, Matsuki T, Mazda O, Kubo T.
  • Organizer: 16th World Congress of the Osteoarthritis Research Society International
  • Place of Presentation: Philadelphia, U.S.A
• [Presentation] The roles of heat shock protein 70 on chondrocyte (2013)
  • Author(s): Matsuki T, Arai Y, Tsuchida S, Terauchi R, Inoue H, Nakagawa S, Inoue A, Mazda O, Kubo T.
  • Organizer: 16th World Congress of the Osteoarthritis Research Society International
  • Place of Presentation: Philadelphia, U.S.A
• [Presentation] 低酸素環境下の軟骨細胞におけるheat shock protein 70の役割 (2012)
  • Author(s): 土田真嗣,新井祐志,寺内 竜,井上裕章,齊藤正純,平岡延之,松田修,久保俊一
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-10-26
• [Presentation] 活性化マクロファージに対するROSを介したランソプラゾールの抗炎症効果の解析
  • Author(s): 市丸昌平，中川周士，新井祐志，土田真嗣，井上裕章，松木智宏，久保俊一
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
• [Presentation] ソノポレーションで導入したTNF-α特異的siRNAによる関節炎モデルの治療効果
  • Author(s): 井上裕章，新井祐志，中川周士，寺内 竜，土田真嗣，松木智宏，井上敦夫，齊藤正純，松田 修，久保俊一
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
• [Presentation] 関節軟骨の分子生物学的研究―ストレス応答を中心に―
  • Author(s): 新井祐志
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
• [Presentation] 活性化マクロファージに対する一酸化窒素の産生抑制によるランソプラゾールの抗炎症効果の解析
  • Author(s): 市丸昌平，中川周士，新井祐志，土田真嗣，井上裕章，松木智宏，谷口大吾，小田 良，藤原浩芳，久保俊一
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
• [Presentation] トレッドミル走行がラット膝関節軟骨に与える影響
  • Author(s): 松木智宏，新井祐志，中川周士，土田真嗣，井上裕章，寺内 竜，井上敦夫，久保俊一
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
• [Presentation] 軟骨細胞に対するストレスが肥大分化関連因子に与える影響
  • Author(s): 井上裕章
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
• [Book] 生体電気・物理刺激による骨・軟部組織修復法(温熱刺激による変形性関節症の進行抑制効果) (2012)
  • Author(s): 新井祐志,土田真嗣,藤田伸弥
  • Total Pages: 304
  • Publisher: 金芳堂