New approach of hyaluronan as osteoarthritis drug and analysis of articular cartilage protection mechanism

• Project/Area Number: 25462372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: Ohtsuki Takashi 岡山大学, 保健学研究科, 非常勤研究員 (10534802)
• Co-Investigator(Kenkyū-buntansha): Hirohata Satoshi 岡山大学, 大学院保健学研究科, 教授 (90332791) ; Nishida Keiichiro 岡山大学, 大学院医歯薬学研究科, 準教授 (80284058)
• Co-Investigator(Renkei-kenkyūsha): Fujibuchi Wataru 京都大学, iPS研究所, 教授 (60273512) ; Shinohata Ryoko 岡山大学, 大学院保健学研究科, 助教 (70335587) ; Kusachi Shozo 岡山大学, 大学院保健学研究科, 特任教授 (30214943) ; Ninomiya Yoshifumi 岡山大学, 大学院医歯薬学研究科, 教授 (70126241)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 軟骨 / マトリックス / ADAMTS / 変形性関節症 / ヒアルロン酸 / メカニカルストレス / 細胞外マトリックス / 医療・福祉

Outline of Final Research Achievements

Detection of miRNAs control cytokine induced aggrecanase We detected several miRNA s using miRNA array technique.Long term hyaluronan (HA) treatment reduced cartilage destruction, significantly, but its protection was limited.We revealed mechanical stress did not change HA receptor genes CD44 and ICAM1 mRNA expression level in chondrosarcoma cell line OUMS-27.Weak mechanical stress induced cartilage matrix proteins, both aggerecan and type 2 collagen in OUMS-27.

Research Products

• [Journal Article] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor (2014)
  • Author(s): Inagaki J, Takahashi K, Ogawa H, Asano K, Faruk Hatipoglu O, Cilek MZ, Obika M, Ohtsuki T, Hofmann M, Kusachi S, Ninomiya Y, Hirohata S
  • Journal Title: Exp Cell Res Volume: 323(2) Issue: 2 Pages: 263-75
  • DOI: 10.1016/j.yexcr.2014.03.002
  • Peer Reviewed / Open Access
• [Presentation] Assesment of therapeutic value of osteoarthritis rehabilitation by molecular biological and biochemical approach (2016)
  • Author(s): Takashi Ohtsuki1, Kanae Kumagishi24, Akira Shinaoka2, Keiichiro Nishida2, Aiji Ootsuka2, Kenichiro Sakata3, Syunsuke Sakata3, Kenji Kawamura4, Satoshi Hirohata1
  • Organizer: 第2回国際リハビリテーションシンポジウムin京都
  • Place of Presentation: 京都大学（杉浦地域医療研究センター）
  • Year and Date: 2016-03-25
  • Int'l Joint Research
• [Presentation] ラット変形性関節症モデルへのヒアルロン酸投与による軟骨保護効果の解析 (2016)
  • Author(s): 大月孝志、品岡玲、熊岸加苗、佐藤未來、金道幸子、長谷川みさ、海原弘貴、浅野恵一、障子友理、稲垣純子、大橋俊孝、西田圭一郎、廣畑聡
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広島（広仁会館）
  • Year and Date: 2016-02-19
• [Presentation] 伸展刺激の強度による細胞外マトリックスタンパクおよびマトリックス分解酵素発現への影響 (2015)
  • Author(s): 大月孝志、金道幸子、長谷川みさ、稲垣純子、浅野恵一、 障子友理、熊岸加苗、西田圭一郎、大橋俊孝、廣畑 聡
  • Organizer: 第38回分子生物学会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸（神戸ポートピアアイランド）
  • Year and Date: 2015-12-01
• [Presentation] ADAMTS1 null mice demonstrated omphalocele phenotype. (2015)
  • Author(s): Satoshi Hirohata, Omer Faruk Hatipoglu, Eriko Kusunoki, Takashi Ohtsuki, Junko Inagaki, Shozo Kusachi, Yoshifumi Ninomiya.
  • Organizer: Gordon Research Conference
  • Place of Presentation: Maine , USA (Sunday River)
  • Year and Date: 2015-08-02
  • Int'l Joint Research
• [Presentation] Biochemical analysis of osteoarthritis conservative therapy-matrix degrading activity in synovial fluid- (2015)
  • Author(s): Kanae Kumagishi-Shinaoka、Takashi Ohtsuki、Satoshi Hirohata、Kenji Kawamyra、Aiji Otsuka 、Kennichiro Sakata、Syunsuke Sakata
  • Organizer: The 28th annual meeting of the Japanese Clinical Orthopaedic Association
  • Place of Presentation: Yamaguchi (KAIKYO MESSE )
  • Year and Date: 2015-07-19
• [Presentation] HYALURONAN TREATMENT REDUCED MATRIX DEGRADATION BOTH IN VITRO AND IN VIVO RAT OSTEOARTHRITIS MODEL. (2015)
  • Author(s): Takashi Ohtsuki, , Yuri Shoji, Keiichi Asano, Aya Hirata, Teruyuki Kawadi, Junko Ingaki, Kanae Kumagishi, Keiichiro Nishida, Toshitaka Oohashi ,Satoshi Hirohata
  • Organizer: 10th International Confewrence HYALURONAN 2015
  • Place of Presentation: Florence (Italy)
  • Year and Date: 2015-06-07
  • Int'l Joint Research
• [Presentation] 腫瘍血管新生における細胞外マトリックス分解の意義 (2015)
  • Author(s): 浅野 恵一、稲垣 純子、障子 友理、Matthias Hofmann、大月 孝志、大橋 俊孝、廣畑 聡
  • Organizer: 第13回がんとハイポキシア研究会
  • Place of Presentation: 静岡（国立遺伝学研究所）
  • Year and Date: 2015-06-05
• [Presentation] Versicanolysis by ADAMTS in tumor angiogenesis (2015)
  • Author(s): Keiichi Asano, Junko Inagaki, Shoji Yuri, Matthias Hofmann, Takashi Ohtsuki, Satoshi Hirohata, Toshitaka Oohashi
  • Organizer: Joint Conference of 47th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR)
  • Place of Presentation: Tokyo（KOKUYO hall ）
  • Year and Date: 2015-05-15
• [Presentation] Moderate mechanical stress differently altered the mRNA expressions of aggrecan, collagen and ADAMTSs in human chondrosarcoma cells. (2015)
  • Author(s): Takashi Ohtsuki, Yukiko Kindo, Misa hasegawa, Aya Hirata, Teruyuki Kawadi, Keiichi Asano, Junko Inagaki, Shoji Yuri, Kanae Kumagishi, Keiichiro Nishida, Toshitaka Oohashi, Satoshi Hirohata,
  • Organizer: Joint Conference of 47th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR)
  • Place of Presentation: Tokyo（KOKUYO hall ）
  • Year and Date: 2015-05-15
• [Presentation] A feasible study of molecular bio-imaging of articular cartilage proteoglycans (2015)
  • Author(s): "Toshitaka Oohashi, Hiroki Kakuta，Manabu Hagaya, Satoshi Hirohata，Shoya Yamada, Yoshifumi Ninomiya，Keiichiro Nishida"
  • Organizer: Joint Conference of 47th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR)
  • Place of Presentation: Tokyo（KOKUYO hall ）
  • Year and Date: 2015-05-15
• [Presentation] Structurally simple cartilage probes constructed with ε-lysine oligomers targeting chondroitin sulfates (2014)
  • Author(s): Hiroki Kakuta, Manabu Hagaya, Shoya Yamada, Yuki Furusawa, Ami Maehara, Satoshi Hirohata, Keiichiro Nishida, Mitsuaki Ono, Takashi Ohtsuki, Yoshifumi Ninomiya, and Toshitaka Oohashi
  • Organizer: 第7回高度医療都市を創出する未来技術国際シンポジウム
  • Place of Presentation: Okayama Okayama university
• [Presentation] ADAMTS1 was differently regulated in breast cancer cells (2014)
  • Author(s): Keiichi asano, Satoshi Hirohata, Masanari Obika, Omer Faruk Hatipoglu, Hiroko Ogawa, Mehmet Zeynel Cilek, Junko Inagaki, Takashi Ohtsuki, Hiroko Ishii, Kunihiko Hatanaka, Shozo Kusachi, Tomoko Yonezawa, Toshitaka Oohashi, Yoshifumi Ninomiya
  • Organizer: 第7回高度医療都市を創出する未来技術国際シンポジウム
  • Place of Presentation: Okayama Okayama university
• [Presentation] Creation of novel articular cartilage specific X-ray imaging probes composed of lysine oligomers (2014)
  • Author(s): Toshitaka Oohashi, Manabu Hagaya, Mitsuaki Ono, Shoya Yamada, Takashi Ohtsuki, Ami Maehara, Satoshi Hirohata, Keiichiro Nishida, Takuo Kuboki, Hiroki Kakuta, Yoshifumu Ninomiya
  • Organizer: The 27th Annual meeting of the Japanese Society of Cartilage metabolism
  • Place of Presentation: (Kyoto) Kyoto Medical Association Center
• [Presentation] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial (2014)
  • Author(s): Junko Inagaki, Katsuyuki Takahashi, Hiroko Ogawa, Omer Hatipoglu, Mehmet Cilek, Masanari Obika,Takashi Ohtsuki, Shozo Kusachi, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: Kyoto (Kyoto Miyakomesse)
• [Presentation] Cyclic tensile strain (CTS) down-regulates interleukin(IL)-1b and Tumor necrosis factor(TNF)-a induced matrix degrading enzymes mRNA expression in human chondrosarcoma cell line OUMS-27 by mechano sensor (2014)
  • Author(s): Takashi Ohtsuki, Teruyuki Kawadi, Aya Hirata, Keiichi Asano, Eriko Kusunoki , Junko Inagaki, Kanae Kumagishi , Keiichiro Nishida , Yoshifumi Ninomiya , Satoshi Hirohata
  • Organizer: The 2nd International Symposium on Mechanobiology (ISMB 2014)
  • Place of Presentation: Okayama(Okayama university Junko Fukutake Hall)
• [Presentation] Short period Hyaluronan treatment reduced cartilage degradation in rat osteoarthritis model. (2014)
  • Author(s): Takashi Ohtsuki, Satoshi Hirohata, Yuri Shoji, Keiichi Asano, Aya Hirata, Teruyuki Kawadi, Junko Ingaki, Kanae Kumagishi, Keiichiro Nishida, Yoshifumi Ninomiya
  • Organizer: Joint Conference of 46th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR), and 61th Annual Meeting of the Japan Matrix Club (JMC)
  • Place of Presentation: Nagoya（Wink Nagoya）
• [Presentation] 変形性膝関節症の保存的治療の効果に関する生化学的解析 (2014)
  • Author(s): 熊岸加苗、大月孝志、酒井孝文、廣畑聡、渡邊徹大、河村顕治、大塚愛二 、坂田賢一郎、坂田俊輔
  • Organizer: 第27回日本臨床整形外科学会学術集会
  • Place of Presentation: 仙台 サンプラザホール
• [Presentation] Hyaluronan protects articular cartilage in a size dependent manner (in vivo and in vitro study) (2013)
  • Author(s): Takashi Ohtsuki, Omer Faruk Hatipoglu, Keiichiro Nishida , Satoshi Hirohata , Yoshifumi Ninomiya
  • Organizer: Joint Conference of 45th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR), and 60th Annual Meeting of the Japan Matrix Club (JMC)
  • Place of Presentation: Wakayama（Wakayama Univ. Lifelong Learing and Medical Community Center）
• [Presentation] 変形性膝関節症への運動・薬物併用療法に関する解析 (2013)
  • Author(s): 熊岸加苗、大月孝志、酒井孝文、廣畑聡、渡邊徹、河村顕治、大塚愛二、坂田俊輔
  • Organizer: 第26回日本臨床整形外科学会学術集会
  • Place of Presentation: 静岡（グランシップ静岡）
• [Presentation] Cyclic tensile strain (CTS) inhibits Interleukin-1beta and Tumor Necrosis Factor-alpha induced catalytic reactions in human chondrosarcoma cell line OUMS-27-microRNA array analysis- (2013)
  • Author(s): Takashi Ohtsuki, Teruyuki Kawadi, Aya Hirata, Keiichi Asano, Eriko Kusunoki , Junko Inagaki, Kanae Kumagishi , Keiichiro Nishida , Yoshifumi Ninomiya , Satoshi Hirohata
  • Organizer: The 36th Annual meeting of the Molecular Biology Society of Japan
  • Place of Presentation: (Kobe) Kobe Conbention Center
• [Remarks] 岡山大学 医歯薬学総合研究科 分子医化学講座
  • URL: http://www.mbb-okayama.com/