The analysis of cellular stress response towards novel conservative therapies for joint disease

• Project/Area Number: 20390404
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• 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, 医学研究科, 教授 (20178031)
• Co-Investigator(Kenkyū-buntansha): ARAI Yuji (TAKAHASHI Kenji) 京都府立医科大学, 医学研究科, 講師 (50347449) ; 高橋 謙治 京都府立医科大学, 医学研究科, 講師 (30347447)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: heat shock protein 70 / ストレス応答機構 / 変形性関節症 / 低酸素 / 温熱 / グルタミン / マイクロウェーブ / 関節疾患 / HSP70 / 低酸素誘導因子 / 骨形成因子

Research Abstract

When heat shock protein 70(HSP70), a molecular chaperone, was induced in chondrocytes as a stress response mechanism under hypoxic condition, the expression of extracellular matrix gene were increased, and the chondrocytes were protected. We developed the efficiently and safe methods that supplementation of glutamine in combination with moderate heat treatment using a microwave applicator induced sufficient increased of HSP70 for therapeutic purposes in vivo. These findings showed that controlling HSP70 expression in the cartilage using supplementation of glutamine in combination with thermotherapy might offer a novel strategy for suppressing cartilage degeneration in osteoarthritis.

Research Products

• [Journal Article] Combined microwave irradiation and intraarticular glutamine administration-induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model (2012)
  • Author(s): Shinya Fujita, Yuji Arai, Shuji Nakagawa, Kenji A. Takahashi, Ryu Terauchi, Atsuo Inoue, Hitoshi Tonomura, Nobuyuki Hiraoka, Hiroaki Inoue, Shinji Tsuchida, Osam Mazda, Toshikazu Kubo
  • Journal Title: Journal of Orthopaedic Reseach Volume: Vol.30 Pages: 401-407
  • URL: http://onlinelibrary.wiley.com/doi/10.1002/jor.21535/abstract
  • Peer Reviewed
• [Journal Article] Combined microwave irradiation and intraarticular glutamine administr ation-induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model (2012)
  • Author(s): Shinya Fujita, Yuji Arai, Shuji Nakagawa, Kenji A.Takahashi, Ryu Terauchi, Atsuo Inoue, Hitoshi Tonomura, Nobuyuki Hiraoka, Hiroaki Inoue, Shinji Tsuchida, Osam Mazda, Toshikazu Kubo
  • Journal Title: JOURNAL OF ORTHOPAEDIC RESEARCH Volume: 30 Pages: 401-407
  • Peer Reviewed
• [Journal Article] N-Acetylcysteine Prevents Nitric Oxide-Induced Chondrocyte Apoptosis and Cartilage Degeneration in an Experimental Model of Osteoarthritis (2010)
  • Author(s): Shuji Nakagawa, Yuji Arai, Osam Mazda, Tsunao Kishida, Kenji A. Takahashi, Kei Sakao, Masazumi Saito, Kuniaki Honjo, Jiro Imanishi, Toshikazu Kubo
  • Journal Title: Journal of Orthopaedic Reseach Volume: Vol.28 Pages: 156-163
  • URL: http://onlinelibrary.wiley.com/doi/10.1002/jor.20976/abstract
  • Peer Reviewed
• [Journal Article] N-Acetylcysteine Prevents Nitric Oxide-Induced Chondrocyte Apoptosis and Cartilage Degeneration in an Experimental Model of Osteoarthritis (2010)
  • Author(s): Shuji Nakagawa, Yuji Arai, Osam Mazda, Tsunao Kishida, Kenji A.Takahashi, Kei Sakao, Masazumi Saito, Kuniaki Honjo, Jiro Imanishi, Toshikazu Kubo
  • Journal Title: JOURNAL OF ORTHOPAEDIC RESEARCH Volume: 28 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Hyperthermia for the treatment of articular cartilage with osteoarthritis (2009)
  • Author(s): Kenji A. Takahashi, Hitoshi Tonomura, Yuji Arai, Ryu Terauchi, Kuniaki Honjo, Nobuyuki Hiraoka, Tatsuya Hojo, Taisuke Kunitomo, Toshikazu Kubo
  • Journal Title: International Journal of Hyperthermia Volume: Vol.25, No8 Pages: 661-667
  • URL: http://informahealthcare.com/doi/abs/10.3109/02656730903107519
  • Peer Reviewed
• [Journal Article] Hyperthermia for the treatment of articular cartilage with osteoarthritis (2009)
  • Author(s): Kenji A Takahashi, Toshikazu Kubo
  • Journal Title: International Journal of Hyperthermia 25(8) Pages: 661-667
  • Peer Reviewed
• [Journal Article] Effects of heat stimulation via microwave applicator on cartilage matrix gene and HSP70 expression in the rabbit knee joint (2008)
  • Author(s): Hitoshi Tonomura, Kenji A. Takahashi, Osam Mazda, Yuji Arai, Masaharu Shin-Ya, Atsuo Inoue, Kuniaki Honjo, Tatsuya Hojo, Jiro Imanishi, Toshikazu Kubo
  • Journal Title: Journal of Orthopaedic Reseach Volume: Vol.26 Pages: 34-41
  • URL: http://onlinelibrary.wiley.com/doi/10.1002/jor.20421/abstract;jsessionid=C846DE7EF515F96FD6959D9EDB20BDBA.d03t02
  • Peer Reviewed
• [Journal Article] Effects of heat stimulation via microwave appliocator on cartilage matrix gene and HSP70 expression in the rabbit knee joint (2008)
  • Author(s): Hitoshi Tonomura, Toshikazu Kubo
  • Journal Title: Journal of Orthopaedic Reseach 26(1) Pages: 34-41
  • Peer Reviewed
• [Presentation] 低酸素環境およびHIF-1αが培養軟骨におけるHSP70と軟骨細胞外基質合成に与える影響 (2011)
  • Author(s): 土田真嗣, 新井祐志, 寺内竜, 本城邦晃, 中川周士, 平岡延之, 井上裕章, 齊藤正純, 松田修, 久保俊一
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: ベイシア文化ホール(群馬県)
  • Year and Date: 2011-10-21
• [Presentation] 低酸素環境がHSP70と軟骨細胞外基質合成に与える影響 (2011)
  • Author(s): 土田真嗣, 新井祐志, 寺内竜, 本城邦晃, 中川周士, 平岡延之, 井上裕章, 齊藤正純, 久保俊一
  • Organizer: 第24回日本軟骨代謝学会
  • Place of Presentation: 九州大学医学部百年講堂(福岡県)
  • Year and Date: 2011-03-05
• [Presentation] Effect of hypoxia on cartilage matrix gene and heat shock protein 70 expression in cultured chondrocytes (2011)
  • Author(s): Shinji Tsuchida, Yuji Arai, Ryu Terauchi, Kuniaki Honjo, Shuji Nakagawa, Nobuyuki Hiraoka, Hiroaki Inoue, Masazumi Saito, Osam Mazda, Tsunao Kishida, Toshikazu Kubo
  • Organizer: 57th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: Long Beach Convention Center(Long Beach, CA, USA)
• [Presentation] Effect of hypoxia on the expression of cartilage matrix gene and heat shock protein 70 in cultured chondrocytes (2011)
  • Author(s): Shinji Tsuchida, Yuji Arai, Ryu Terauchi, Kuniaki Honjo, Hiroaki Inoue, Masazumi Saito, Osam Mazda, Toshikazu Kubo
  • Organizer: 14th World Congress of the Osteoarthritis Research Society International(OARSI)
  • Place of Presentation: Hilton San Diego Bayfront(San Diego, CA, USA)
• [Presentation] Effect of hypoxia on cartilage matrix gene and heat shock protein 70 expression in cultured chondrocytes (2011)
  • Author(s): Tsuchida S, Arai Y, Terauchi R, Honjo K, Nakagawa S, Hiraoka N, Inoue H, Saito M, Mazda O, Kishida T, Kubo T
  • Organizer: 57th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: Long Beach Convention Center (Long Beach, CA)
• [Presentation] Effect of hypoxia on the expression of cartilage matrix gene and heat shock protein 70 in cultured chondrocytes (2011)
  • Author(s): Tsuchida S, Arai Y, Terauchi R, Honjo K, Inoue H, Saito M, Mazda O, Kubo T
  • Organizer: 14th World Congress of the Osteoarthritis Research Society International (OARSI)
  • Place of Presentation: Hilton San Diego Bayfront (San Diego, CA)
• [Remarks]
  • URL: http://www.kpu-m.ac.jp/k/orthoped/about/clinic.html