Aggrecanase regulation system in osteoarthritis and strategy for early diagnosis and therapy for osteoarthritis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390399
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: HIROHATA Satoshi Okayama University, 大学院・医歯薬学総合研究科, 助教 (90332791)
• Co-Investigator(Kenkyū-buntansha): NINOMIYA Yoshifumi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (70126241) ; NARUSE Keiji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (40252233) ; OOHASHI Toshitaka 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (50194262) ; NISHIDA Keiichiro 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (80284058)
• Project Period (FY): 2008 – 2010
• Keywords: 関節炎 / ADAMTS

Research Abstract

We analyzed ADAMTS9 single nucleotide polymorphism in arthritis patients. We identified the NF-κB binding to the ADAMTS9 promoter. When mechanical stress was loaded to the cells, the expression of ADAMTS1, 4, 5, 9 were differently induced. In addition, COL1A1 was increased and this induction was mediated by integrin. Mechanical stress induced MMP-13 and ADAMTS5 mRNA and two molecules (RUNX-2 and p38MAPK) play important roles.

Research Products

• [Journal Article] Ischemia-induced angiogenesis is impaired in aminopeptidase A deficient mice via down-regulation of HIF-1α. (2011)
  • Author(s): Kubota R, Numaguchi Y, Ishii M, Niwa M, Okumura K, Naruse K, Murohara T
  • Journal Title: Biochem Biophys Res Commun in press
  • Peer Reviewed
• [Journal Article] In-vitro culture with a tilting device in chemically defined media during meiotic maturation and early development improves the quality of blastocysts derived from In-vitro matured and fertilized porcine oocytes. (2011)
  • Author(s): Koike T, Matsuura K, Koike T, Matsuura K, Naruse K, Funahashi H
  • Journal Title: J Reprod in press
  • Peer Reviewed
• [Journal Article] Olmesartan reduces arterial stiffness and serum adipocyte fatty acid-binding protein in hypertensive patients. (2011)
  • Author(s): Miyoshi T, Doi M, Hirohata S, Kamikawa S, Usui S, Ogawa H, Sakane K, Izumi R, Ninomiya Y, Kusachi S.
  • Journal Title: Heart Vessels in press
  • Peer Reviewed
• [Journal Article] Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells. (2011)
  • Author(s): Tetsunaga T, Nishida K, Furumatsu T, Naruse K, Hirohata S, Yoshida A, Saito T, Ozaki T.
  • Journal Title: Osteoarthritis Cartilage. 19(2) Pages: 222-232
  • Peer Reviewed
• [Journal Article] Association of serum levels of arachidonic acid and eicosapentaenoic acid with prevalence of major adverse cardiac events after acute myocardial infarction (2011)
  • Author(s): Ueeda M, Doumei T, Takaya Y, Ohnishi N, Takaishi A, Hirohata S, Miyoshi T, Shinohata R, Usui S, Kusachi S.
  • Journal Title: Heart Vessels 26(2) Pages: 145-152
  • Peer Reviewed
• [Journal Article] AHR, a novel acute hypoxia-response sequence, drives reporter gene under hypoxia in vitro and in vivo. (2011)
  • Author(s): Cilek MZ, Hirohata S, Hatipoglu OF, Ogawa H, Miyoshi T, Inagaki J, Ohtsuki T, Harada H, Kamikawa S, Kusachi S, Ninomiya Y.
  • Journal Title: Cell Biol Int. 35 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Connective tissue growth factor induction in a pressure-overloaded heart ameliorated by the angiotensin II type 1 receptor blocker olmesartan. (2010)
  • Author(s): Iwamoto M, Hirohata S, Ogawa H, Ohtsuki T, Shinohata R, Miyoshi T, Hatipoglu FO, Kusachi S, Yamamoto K, Ninomiya Y.
  • Journal Title: Hypertens Res. 33(12) Pages: 1305-1311
  • Peer Reviewed
• [Journal Article] Significant relationship between changes in brachial-ankle pulse wave velocity relative to blood pressure elevation and coronary artery disease (2010)
  • Author(s): Komatsubara I, Inoue S, Koumoto R, Matano S, Kitawaki T, Hirohata S, Miyoshi T, Ogawa H, Shinohata R, Kusachi S.
  • Journal Title: Coron Artery Dis. 21(7) Pages: 407-413
  • Peer Reviewed
• [Journal Article] Effect of cilnidipine on normal to marginally elevated urine albumin-creatinine ratio in asymptomatic non-diabetic hypertensive patients : an exponential decay curve analysis. (2010)
  • Author(s): Nakatsu T, Toyonaga S, Mashima K, Yuki Y, Nishitani A, Ogawa H, Miyoshi T, Hirohata S, Izumi R, Kusachi S.
  • Journal Title: Clin Drug Investig. 30(10) Pages: 699-706
  • Peer Reviewed
• [Journal Article] Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis. (2010)
  • Author(s): Kawabata T, Nishida K, Takasugi K, Ogawa H, Sada K, Kadota Y, Inagaki J, Hirohata S, Ninomiya Y, Makino H.
  • Journal Title: Arthritis Res Ther. 12(4): Pages: R133
  • Peer Reviewed
• [Journal Article] Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound. Atherosclerosis. (2010)
  • Author(s): Miyoshi T, Onoue G, Hirohata A, Hirohata S, Usui S, Hina K, Kawamura H, Doi M, Kusano KF, Kusachi S, Ninomiya Y.
  • Journal Title: Atherosclerosis. 211(1) Pages: 164-169
  • Peer Reviewed
• [Journal Article] Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients. (2010)
  • Author(s): Doi M, Miyoshi T, Hirohata S, Kamikawa S, Usui S, Kaji Y, Sakane K, Ogawa H, Ninomiya Y, Kusachi S.
  • Journal Title: Am J Med Sci. 339(5) Pages: 433-439
  • Peer Reviewed
• [Journal Article] Type IV collagen induces expression of thrombospondin-1 that is mediated by integrin alpha1 beta1 in astrocytes. (2010)
  • Author(s): Yonezawa T, Hattori S, Inagaki J, Kurosaki M, Takigawa T, Hirohata S, Miyoshi T, Ninomiya Y.
  • Journal Title: Glia. 58(7) Pages: 755-767
  • Peer Reviewed
• [Journal Article] Cardio-ankle vascular index is independently associated with the severity of coronary atherosclerosis and left ventricular function in patients with ischemic heart disease. (2010)
  • Author(s): Miyoshi T, Doi M, Hirohata S, Sakane K, Kamikawa S, Kitawaki T, Kaji Y, Kusano KF, Ninomiya Y, Kusachi S.
  • Journal Title: J Atheroscler Thromb. 17(3) Pages: 249-258
  • Peer Reviewed
• [Journal Article] Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis : evaluation by intravascular ultrasound) trial. (2010)
  • Author(s): Hirohata A, Yamamoto K, Miyoshi T, Hatanaka K, Hirohata S, Yamawaki H, Komatsubara I, Murakami M, Hirose E, Sato S, Ohkawa K, Ishizawa M, Yamaji H, Kawamura H, Kusachi S, Murakami T, Hina K, Ohe T.
  • Journal Title: J Am Coll Cardiol. 55(10) Pages: 976-982
  • Peer Reviewed
• [Journal Article] A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression by chondrocytes during endochondral ossification. (2009)
  • Author(s): Kumagishi K, Nishida K, Yamaai T, Momota R, Miyaki S, Hirohata S, Naito I, Asahara H, Ninomiya Y, Ohtsuka A.
  • Journal Title: Arch Histol Cytol. 72(3) Pages: 175-185
  • Peer Reviewed
• [Journal Article] Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis. (2009)
  • Author(s): Ayada K, Yokota K, Hirai K, Fujimoto K, Kobayashi K, Ogawa H, Hatanaka K, Hirohata S, Yoshino T, Shoenfeld Y, Matsuura E, Oguma K.
  • Journal Title: Lupus. 18(13) Pages: 1154-1168
  • Peer Reviewed
• [Journal Article] Human eosinophil cationic protein enhances stress fiber formation in Balb/c 3T3 fibroblasts and differentiation of rat neonatal cardiomyocytes. (2009)
  • Author(s): Fukuda T, Iwata M, Kitazoe M, Maeda T, Salomon D, Hirohata S, Tanizawa K, Kuroda S, Seno M
  • Journal Title: Growth Factors. 27(4) Pages: 228-236
  • Peer Reviewed
• [Journal Article] Augmentation index is associated with B-type natriuretic peptide in patients with paroxysmal atrial fibrillation. (2009)
  • Author(s): Kaji Y, Miyoshi T, Doi M, Hirohata S, Kamikawa S, Sakane K, Kitawaki T, Kusachi S, Kusano KF, Ito H.
  • Journal Title: Hypertens Res. 32(7) Pages: 611-616
  • Peer Reviewed
• [Journal Article] ADAMTS1 is a unique hypoxic early response gene expressed by endothelial cells. (2009)
  • Author(s): Hatipoglu OF, Hirohata S, Cilek MZ, Ogawa H, Miyoshi T, Obika M, Demircan K, Shinohata R, Kusachi S, Ninomiya Y.
  • Journal Title: J Biol Chem. 284(24) Pages: 16325-16333
  • Peer Reviewed
• [Journal Article] Stress-Axis Regulated Exon (STREX) in the C terminus of BK(Ca) channels is responsible for the stretch sensitivity. (2009)
  • Author(s): Naruse K, Tang QY, Sokabe M
  • Journal Title: Biochem Biophys Res Commun 385(4) Pages: 634-639
  • Peer Reviewed
• [Journal Article] Increased mRNA expression of ADAMTS metalloproteinases in metastatic foci of head and neck cancer. (2009)
  • Author(s): Demircan K, Gunduz E, Gunduz M, Beder LB, Hirohata S, Nagatsuka H, Cengiz B, Cilek MZ, Yamanaka N, Shimizu K, Ninomiya Y.
  • Journal Title: Head Neck 31(6) Pages: 793-801
  • Peer Reviewed
• [Journal Article] The 3'-untranslated Region of ADAMTS1 Regulates Its mRNA Stability (2009)
  • Author(s): Hatipoglu OF, Hirohata S, Yaykasli KO, Cilek MZ, Demircan K, Shinohata R, Yonezawa T, Oohashi T, Kusachi S, Ninomiya Y.
  • Journal Title: Acta Medica Okayama 63(2) Pages: 79-85
  • Peer Reviewed
• [Journal Article] ADAMTS9 activation by interleukin 1beta via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. (2009)
  • Author(s): Yaykasli KO, Oohashi T, Hirohata S, Hatipoglu OF, Inagawa K, Demircan K, Ninomiya Y.
  • Journal Title: Mol Cell Biochem. 323(1-2) Pages: 69-79
  • Peer Reviewed
• [Journal Article] Increased Augmentation Index of the Radial Pressure Waveform in Patients with Paroxysmal Atrial Fibrillation. (2009)
  • Author(s): Doi M, Miyoshi T, Hirohata S, Iwabu A, Tominaga Y, Kaji Y, Kamikawa S, Sakane K, Kitawaki T, Kusano KF, Kusachi S.
  • Journal Title: Cardiology 113(2) Pages: 138-145
  • Peer Reviewed
• [Journal Article] Relationship between activin A level and infarct size in patients with acute myocardial infarction undergoing successful primary coronary intervention. (2009)
  • Author(s): Miyoshi T, Hirohata S, Uesugi T, Hirota M, Ohnishi H, Nogami K, Hatanaka K, Ogawa H, Usui S, Kusachi S.
  • Journal Title: Clin Chim Acta. 401(1-2) Pages: 3-7
  • Peer Reviewed
• [Journal Article] Hyaluronan receptors involved in cytokine induction in monocytes. (2009)
  • Author(s): Yamawaki H, Hirohata S, Miyoshi T, Takahashi K, Ogawa H, Shinohata R, Demircan K, Kusachi S, Yamamoto K, Ninomiya Y.
  • Journal Title: Glycobiology. 19(1) Pages: 83-92
  • Peer Reviewed
• [Journal Article] Analysis of cyclic-stretching responses using cell-adhesion-patterned cells. (2008)
  • Author(s): Katanosaka Y, Bao JH, Komatsu T, Suemori T, Yamada A, Mohri S, Naruse K
  • Journal Title: J Biotechnol 133(1) Pages: 82-89
  • Peer Reviewed
• [Journal Article] Association of new arterial stiffness parameter, the cardio-ankle vascular index, with left ventricular diastolic function. (2008)
  • Author(s): Sakane K, Miyosh T, Doi M, Hirohata S, Kaji Y, Kamikawa S, Ogawa H, Hatanaka K, Kitawaki T, Kusachi S, Yamamoto K.
  • Journal Title: J Atheroscler Thromb 15(5) Pages: 261-268
  • Peer Reviewed
• [Journal Article] Serum N-3 Polyunsaturated Fatty Acid Levels Correlate With the Extent of Coronary Plaques and Calcifications in Patients With Acute Myocardial Infarction. (2008)
  • Author(s): Ueeda M, Doumei T, Takaya Y, Shinohata R, Katayama Y, Ohnishi N, Takaishi A, Miyoshi T, Hirohata S, Kusachi S.
  • Journal Title: Circ J 72(11) Pages: 1836-1843
  • Peer Reviewed
• [Journal Article] Association of corrected QT dispersion with symptoms improvement in patients receiving cardiac resynchronization therapy. (2008)
  • Author(s): Hina K, Kawamura H, Murakami T, Yamamoto K, Yamaji H, Murakami M, Hirohata S, Ogawa H, Sakane K, Kusachi S.
  • Journal Title: Heart Vessels. 23(5) Pages: 325-333
  • Peer Reviewed
• [Journal Article] Prone Position is Essential for Detection of Pulmonary Vein Pseudostenosis by Enhanced Multidetector Computed Tomography in Patients Who Undergo Pulmonary Vein Isolation. (2008)
  • Author(s): Yamaji H, Hina K, Kawamura H, Murakami T, Murakami M, Yamamoto K, Hirohata A, Miyoshi T, Hirohata S, Kusachi S.
  • Journal Title: Circ J. 72(9) Pages: 1460-1664
  • Peer Reviewed
• [Journal Article] siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration. (2008)
  • Author(s): Petersen EJ, Miyoshi T, Yuan Z, Hirohata S, Li JZ, Shi W, Angle JF.
  • Journal Title: Atherosclerosis. 198(2) Pages: 301-306
  • Peer Reviewed
• [Journal Article] Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model. (2008)
  • Author(s): Nasu Y, Nishida K, Miyazawa S, Manabe H, Komiyama T, Kadota Y, Yoshida A, Abe N, Hirohata S, Ohtsuka A, Ozaki T.
  • Journal Title: Osteoarthritis and Cartilage 16(6): Pages: 723-732
  • Peer Reviewed
• [Presentation] ヒアルロン酸分子量とアグリカナーゼ発現抑制効果に関する検討 (2011)
  • Author(s): 大月孝志
  • Organizer: 第24回日本軟骨代謝学会
  • Place of Presentation: 福岡市
  • Year and Date: 20110304-20110305
• [Presentation] ADAMTS1プロモーターは急性低酸素応答性に遺伝子を発現する (2011)
  • Author(s): 廣畑聡
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 札幌市
  • Year and Date: 20110129-20110130
• [Presentation] ADAMTS1 inhibit angiogenesis by inducing apoptosis in endothelial cells : in vitro and in vivo study. (2011)
  • Author(s): Masanari Obika
  • Organizer: 第4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: 岡山市
  • Year and Date: 2011-02-08
• [Presentation] 新規急性低酸素応答配列を用いた遺伝子発現ベクターによる急性低酸素下のレポーター遺伝子の発現様式BMB2010 (2010)
  • Author(s): Omer F.Hatipoglu
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] Cd44 Contributes to the Development of Abdominal Aortic Aneurysm in Mice Through the Interaction With Hyaluronic Acid and the Recruitment of Macrophages. (2010)
  • Author(s): Toru Miyoshi
  • Organizer: アメリカ心臓協会(AHA)学術集会
  • Place of Presentation: アメリカ・シカゴ
  • Year and Date: 20101113-20101117
• [Presentation] ADAMTS1遺伝子治療はプロテアーゼ非依存的に血管新生阻害効果を発揮し、腫瘍増大を阻害する (2010)
  • Author(s): 廣畑聡
  • Organizer: 第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
  • Place of Presentation: 秋田市
  • Year and Date: 20100819-20100820
• [Presentation] ADAMTS1のin vitroでのリンパ管新生阻害効果 (2010)
  • Author(s): 稲垣純子
  • Organizer: 第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
  • Place of Presentation: 秋田市
  • Year and Date: 20100819-20100820
• [Presentation] Hatipoglu, ADAMTS1の内皮細胞に対するアポトーシス効果の検討 (2010)
  • Author(s): Omer F.
  • Organizer: 第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
  • Place of Presentation: 秋田市
  • Year and Date: 20100819-20100820
• [Presentation] ADAMTS1プロモーターは急性低酸素状態の内皮細胞選択的に遺伝子発現を誘導する (2010)
  • Author(s): Mehmet Zeynel Cilek
  • Organizer: 第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
  • Place of Presentation: 秋田市
  • Year and Date: 20100819-20100820
• [Presentation] プロテアーゼ活性に依存しない血管内皮細胞への作用によりADAMTS1は腫瘍発育を阻害する (2010)
  • Author(s): 廣畑聡
  • Organizer: 第7回日本病理学会カンファレンス
  • Place of Presentation: 岡山市
  • Year and Date: 20100806-20100807
• [Presentation] ADAMTS1 is a Novel Biomarker for Acute ischemia/reperfusion in Myocardial infarction Patients. (2010)
  • Author(s): 廣畑聡
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 福岡市
  • Year and Date: 20100305-20100507
• [Presentation] ADAMTS1 is an endothelial cell-specific hypoxia- inducible gene. (2009)
  • Author(s): 廣畑聡
  • Organizer: アメリカ心臓協会(AHA)学術集会
  • Place of Presentation: アメリカ・オーランド
  • Year and Date: 20091114-20091118
• [Presentation] HIF-1 Directly Induced Novel Metalloproteinase ADAMTS1 Expression and ADAMTS1 under Hypoxia Accelerated Endothelial Cell Migration. (2009)
  • Author(s): 廣畑聡
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 20090620-20090622
• [Presentation] Gene transfer of ADAMTS1 induced apoptosis in endothelial cells and inhibited tumor growth. (2009)
  • Author(s): 廣畑聡
  • Organizer: PPCTSS (PanPacific Connective Tissue Society Symposium)
  • Place of Presentation: 横須賀市
  • Year and Date: 20090604-20090607
• [Presentation] Hatipoglu, ADAMTS1 is induced by hypoxia in endothelial cells and HIF-1 binds to the ADAMTS1 promoter. (2009)
  • Author(s): Omer F.
  • Organizer: PPCTSS (PanPacific Connective Tissue Society Symposium)
  • Place of Presentation: 横須賀市
  • Year and Date: 20090604-20090607
• [Presentation] ADAMTS1 as a hypoxia sensing biomarker. (2009)
  • Author(s): Mehmet Z.Cilek
  • Organizer: PPCTSS (PanPacific Connective Tissue Society Symposium)
  • Place of Presentation: 横須賀市
  • Year and Date: 20090604-20090607
• [Presentation] The 3'-untranslated Region of ADAMTS1 Regulates Its Expression. (2009)
  • Author(s): Omer F.Hatipoglu
  • Organizer: The 3rd International Congress of Molecular Medicine
  • Place of Presentation: Istanbul, Turkey.
  • Year and Date: 20090505-20090508
• [Presentation] Utilization Of ADAMTS1 As A New Tool For Detecting Hypoxia. (2009)
  • Author(s): Mehmet Z.Cilek
  • Organizer: The 3rd International Congress of Molecular Medicine
  • Place of Presentation: Istanbul, Turkey.
  • Year and Date: 20090505-20090508
• [Presentation] Identification of NF-κB binding elements in human ADAMTS9 promoter. (2009)
  • Author(s): Kadir Demircan
  • Organizer: The 3rd International Congress of Molecular Medicine
  • Place of Presentation: Istanbul, Turkey.
  • Year and Date: 20090505-20090508
• [Remarks] ホームページURL
  • URL: http://mbb-okayama.sakura.ne.jp/
• [Patent(Industrial Property Rights)] 再灌流療法の治療効果を判定する方法 (2009)
  • Inventor(s): 廣畑聡、臼井真一、草地省蔵
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 国際特許PCT出願・PCT/JP2009/069224
  • Filing Date: 2009-11-11
• [Patent(Industrial Property Rights)] 新規DNA断片およびその用途 (2009)
  • Inventor(s): 廣畑聡、二宮善文、草地省蔵、オメル ファルク ハティポール
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 国際特許出願・PCT/JP2009/051907
  • Filing Date: 2009-04-02
• [Patent(Industrial Property Rights)] 再灌流療法の治療効果を判定する方法 (2008)
  • Inventor(s): 廣畑聡、臼井真一、草地省蔵
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 特許出願・特願,2008-289118
  • Filing Date: 2008-11-11
• [Patent(Industrial Property Rights)] 急性虚血性疾患の診断薬 (2008)
  • Inventor(s): 廣畑聡、臼井真一、草地省蔵
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 特許・特許,第4195492号
  • Acquisition Date: 2008-10-03