Aquaporins expression in fibroblast like synoviocytes from OA and RA patients

• Project/Area Number: 24592272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya City University
• Principal Investigator: OTSUKA Takanobu 名古屋市立大学, 医学(系)研究科(研究院), 教授 (10185316)
• Co-Investigator(Kenkyū-buntansha): NAGAYA Yuko 名古屋市立大学, 大学院医学研究科, 教授 (90291583) ; ASAI Kiyofumi 名古屋市立大学, 大学院医学研究科, 教授 (70212462)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節水症 / 関節リウマチ / 変形性膝関節症 / 滑膜組織 / 線維芽細胞様滑膜細胞 / アクアポリン / TNF alfa / RT-PCR / ヒアルロン酸

Outline of Final Research Achievements

Aquaporins (AQPs) are usually present at the plasma membrane, where they regulate the influx and outflow of water and small molecules. We screened for the expression of 12 AQP mRNAs (AQP1-AQP12) in the synovial tissues of patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and examined the patterns of expression in those with and without hydrarthrosis. AQP1, AQP3 and AQP9 were expressed in synovial tissues from patients with OA and RA. Fibroblast-like synoviocytes (FLSs) from patients with RA and OA were cultured and stimulated with TNF-α. AQP9 mRNA expression was strongly induced by TNF-α in FLSs, whereas expression of AQP1 and AQP3 mRNAs was not influenced by TNF-α. Treatment of hyaluronic acid did not affected AQP9 mRNA expression induced by TNF-α. Although the functions of AQP1, AQP3 and AQP9 in synovial tissues remain to be elucidated, AQP9 might play a role in hydrarthrosis and inflammatory synovitis.

Research Products

• [Journal Article] Rac limits TGF-β-induced VEGF synthesis in osteoblasts. Mol Cell Endocrinol. (2015)
  • Author(s): Yamamoto N, Otsuka T, Kondo A, Matsushima-Nishiwaki R, Kuroyanagi G, Kozawa O, Tokuda H.
  • Journal Title: Mol Cell Endocrinol Volume: 405 Pages: 35-41
  • DOI: 10.1016/j.mce.2015.02.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions. (2014)
  • Author(s): Nomura T, Aoyama M, Waguri-Nagaya Y, Goto Y, Suzuki M, Miyazawa K, Asai K, Goto S.
  • Journal Title: Exp Cell Res Volume: 321 Issue: 2 Pages: 167-177
  • DOI: 10.1016/j.yexcr.2013.11.020
  • Peer Reviewed
• [Journal Article] Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. (2014)
  • Author(s): Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, Matsumoto Y, Yamamoto T, Umeda K, Heike T, Okumura N, Koizumi N, Sato T, Nakahata T, Saito M, Otsuka T, Kinoshita S, Ueno M, Ikeya M, Toguchida J.
  • Journal Title: PLOS ONE Volume: 9 Issue: 12 Pages: e112291-e112291
  • DOI: 10.1371/journal.pone.0112291
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Down-regulation by resveratrol of basic fibroblast growth factor-stimulated osteoprotegerin synthesis through suppression of Akt in osteoblasts. (2014)
  • Author(s): Kuroyanagi G, Otsuka T, Yamamoto N, Matsushima-Nishiwaki R, Nakakami A, Mizutani J, Kozawa O, Tokuda H.
  • Journal Title: Int J Mol Sci. Volume: 15 Issue: 5 Pages: 17886-900
  • DOI: 10.3892/ijmm.2014.1934
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cigarette smoke condensate extracts induce IL-1 beta production from rheumatoid arthritis patient-derived synoviocytes, but not osteoarthritis patient-derived synoviocytes, through aryl hydrocarbon receptor-dependent NF-kappa B activation and novel NF-kappa B sites. (2013)
  • Author(s): Adachi M, Okamoto S, Chujyo S, Arakawa T, Yokoyama M, Yamada K, Hayashi A, Akita K, Takeno M, Ito S, Takii T, Waguri-Nagaya Y, Otsuka T, Hayakawa K, Miyazawa K, Onozaki K.
  • Journal Title: J Interferon & Cytokine Research Volume: 33 Issue: 6 Pages: 297-307
  • DOI: 10.1089/jir.2012.0107
  • Peer Reviewed
• [Journal Article] Unphosphorylated heat shock protein 27 suppresses fibroblast growth factor-2-stimulated vascular endothelial growth factor release in osteoblasts. (2013)
  • Author(s): Kondo A, Tokuda H, Matsushima-Nishiwaki R, Kato K, Kuroyanagi G, Mizutani J, Fukuoka M, Wada I, Kozawa O, Otsuka T.
  • Journal Title: Mol Med Rep Volume: 8 Issue: 2 Pages: 691-695
  • DOI: 10.3892/mmr.2013.1533
  • Peer Reviewed
• [Journal Article] Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells. (2013)
  • Author(s): Hayakawa K, Ikeya M, Fukuta M, Woltjen K, Tamaki S, Takahara N, Kato T Jr, Sato S, Otsuka T, Toguchida J
  • Journal Title: Biochem Biophys Res Commun Volume: 432 Issue: 4 Pages: 713-719
  • DOI: 10.1016/j.bbrc.2013.01.003
  • Peer Reviewed
• [Journal Article] Rho-kinase negatively regulates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts. (2013)
  • Author(s): Kondo A, Tokuda H, Kato K, Matsushima-Nishiwaki R, Kuroyanagi G, Mizutani J, Kozawa O, Otsuka T.
  • Journal Title: Biochimie Volume: 95 Issue: 4 Pages: 719-24
  • DOI: 10.1016/j.biochi.2012.10.020
  • Peer Reviewed
• [Journal Article] Cigarette smoke condensate extracts induce IL-1beta production from rheumatoid arthritis patient-derived synoviocytes, but not osteoarthritis patient-derived synoviocytes, through aryl hydrocarbon receptor-dependent NF-kappa B activation and novel NF-kappa B sites. (2013)
  • Author(s): Adachi M, Okamoto S, Chujyo S, Arakawa T, Yokoyama M, Yamada K, Hayashi A, Akita K, Takeno M, Ito S, Takii T, Waguri-Nagaya Y, Otsuka T, Hayakawa K, Miyazawa K, Onozaki K.
  • Journal Title: J Interferon & Cytokine Research Volume: March
  • Peer Reviewed
• [Journal Article] The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes. (2012)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Kikuchi K, Yamagami T, Nozaki M, Aoyama M, Asai K,Otsuka T.
  • Journal Title: Arthritis Res Ther. Volume: 14 Issue: 2 Pages: R87-R87
  • DOI: 10.1186/ar3811
  • Peer Reviewed
• [Journal Article] Wnt3a upregulates prostaglandin F2α-stimulated vascular endothelial growth factor synthesis in osteoblasts. (2012)
  • Author(s): Kondo A, Tokuda H, Mizutani J, Matsushima-Nishiwaki R, Kozawa O, Otsuka T.
  • Journal Title: Mol Med Report. Volume: 6 Issue: 2 Pages: 421-425
  • DOI: 10.3892/mmr.2012.916
  • Peer Reviewed
• [Journal Article] AMPK limits IL-1-stimulated IL-6 synthesis in osteoblasts: involvement of IκB/NF-κB pathway. (2012)
  • Author(s): Kato K, Tokuda H, Matsushima-Nishiwaki R, Natsume H, Kondo A, Ito Y, Kozawa O, Otsuka T.
  • Journal Title: Cell Signal Volume: 24 Issue: 8 Pages: 1706-1712
  • DOI: 10.1016/j.cellsig.2012.04.012
  • Peer Reviewed
• [Presentation] The inhibitory effect of synthetic disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes. (2015)
  • Author(s): Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Fiera Roma (Roma, Italy)
  • Year and Date: 2015-06-10 – 2015-06-13
• [Presentation] A Role For P38 Mitogen-Activated Protein Kinase (Mapk) In Gliostatin Production In Rheumatoid Fibroblast-Like Synoviocytes. (2015)
  • Author(s): Ikuta K, Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Fiera Roma (Roma, Italy)
  • Year and Date: 2015-06-10 – 2015-06-13
• [Presentation] The importance of gliostatin as an indicator of disease activity in patients with rheumatoid arthritis. (2014)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Tatematsu N, Kawaguchi Y, Kobayashi M, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris (Paris, France)
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] Gliostatin regulates vascular endothelial growth-factor production in human fibroblast-like synoviocytes. (2014)
  • Author(s): Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris (Paris, France)
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] The importance of gliostatin as an indicator of disease activity in patients with rheumatoid arthritis. (2014)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Tatematsu N, Kawaguchi Y, Kobayashi M, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress Of Rheumatology
  • Place of Presentation: Le Palais des Congress de Paris (Paris, FRANCE)
• [Presentation] Gliostatin regulates vascular endothelial growth-factor production in human fibroblast-like synoviocytes. (2014)
  • Author(s): Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress Of Rheumatology
  • Place of Presentation: Le Palais des Congress de Paris (Paris, FRANCE)
• [Presentation] The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes (2013)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Terazawa M, Aoyama M, Asai K, Kobayashi M, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: IFEMA's Convention and Congress Centres (Madrid, SPAIN)
• [Presentation] Aquaporin expression in the synovial tissues of patients with osteoarthritis and rheumatoid arthritis. (2013)
  • Author(s): Tatematsu N, Waguri-Nagaya Y, Nagahara M, Ikuta K, Aoyama M, Asai K, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: IFEMA's Convention and Congress Centres (Madrid, SPAIN)
• [Presentation] Aquaporin expression in the synovial tissues of patients with osteoarthritis and rheumatoid arthritis (2013)
  • Author(s): Naoe Tatematsu, Yuko Waguri-Nagaya, Masashizu Nagahara, Kenji Ikuta, Mineyoshi Aoyama, Kiyofumi Asai and Takanobu Otsuka
  • Organizer: EULAR
  • Place of Presentation: Feria de Madrid (Madrid)