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Inflammatory-independent pain mechanism via to VEGF/neuropeptide axis

Research Project

Project/Area Number 18K09119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionKitasato University

Principal Investigator

Takaso Masashi  北里大学, 医学部, 教授 (90439117)

Co-Investigator(Kenkyū-buntansha) 内田 健太郎  北里大学, 医学部, 講師 (50547578)
大久保 直  北里大学, 医学部, 准教授 (10450719)
岩瀬 大  北里大学, 医学部, 助教 (30406946)
井上 玄  北里大学, 医学部, 准教授 (80594209)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血管内皮増殖因子 / 疼痛 / 神経ペプチド / Apelin / 血管内皮成長因子 / TGF-β / 古典経路 / 非古典経路 / ゲノム編集 / 変形性膝関節症 / 非炎症性
Outline of Final Research Achievements

Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear. We investigated the role of VEGF in the osteoarthritic pain pathway. Expression levels of VEGF were positively correlated with pain score, VAS. VEGF-positive cells were identified in the lining of the synovium. Expression of apelin mRNA and protein were significantly elevated in synovial cells treated with exogenous VEGF. Synovial apelin expression levels correlate with VAS. TGF-beta regulated VEGF expression through the canonical and non-canonical pathway. TGF/VEGF/Apelin axis play an important role for inflammation-independent pain in patients with osteoarthritis.

Academic Significance and Societal Importance of the Research Achievements

疼痛の慢性化による我が国の経済損失は3,700億円と推定されており、疼痛治療法メカニズムの解明および疼痛治療法の開発は、社会的、経済的基盤の改善に極めて重要な意義を持っている。本研究成果は、血管内皮増殖因子(VEGF)の上流ならびに下流を標的とした変形性関節症患者の疼痛治療の新たな治療標的を供給するもである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Expression and regulation of macrophage-inducible C-type lectin in human synovial macrophages2020

    • Author(s)
      Moriya M, Uchida K, Takano S, Iwase D, Inoue G, Mukai M, Tazawa R, Aikawa J, Sekiguchi H, Takaso M
    • Journal Title

      Cent Eur J Immunol

      Volume: 45 Issue: 4 Pages: 377-381

    • DOI

      10.5114/ceji.2020.103411

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee2020

    • Author(s)
      Takata K, Uchida K, Mukai M, Takano S, Aikawa J, Iwase D, Sekiguchi H, Miyagi M, Inoue G, Takaso M
    • Journal Title

      Diabetes Metab Syndr Obes

      Volume: 13 Pages: 1491-1497

    • DOI

      10.2147/dmso.s253147

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular endothelial growth factor is regulated by the canonical and non-canonical transforming growth factor-β pathway in synovial fibroblasts derived from osteoarthritis patients2019

    • Author(s)
      Takano S, Uchida K, Shoji S, Itakura M, Iwase D, Aikawa J, Mukai M, Sekiguchi H, Inoue G, Takaso M.
    • Journal Title

      Biomed Res Int

      Volume: - Pages: 6959056-6959056

    • DOI

      10.1155/2019/6959056

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis2018

    • Author(s)
      Takano S, Uchida K, Inoue G, Matsumoto T, Aikawa J, Iwase D, Mukai M, Miyagi M, Takaso M
    • Journal Title

      BMC Musculoskelet Disord

      Volume: 19 Issue: 1 Pages: 204-204

    • DOI

      10.1186/s12891-018-2127-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis2018

    • Author(s)
      Aikawa J, Uchida K, Takano S, Inoue G, Iwase D, Miyagi M, Mukai M, Shoji S, Sekiguchi H, Takaso M
    • Journal Title

      Lipid in health and disease

      Volume: 17 Issue: 1 Pages: 215-215

    • DOI

      10.1186/s12944-018-0864-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Down-regulation of microsomal prostaglandin E2 synthase-1 in the infrapatellar fat pad of osteoarthritis patients with hypercholesterolemia2018

    • Author(s)
      Mukai M, Uchida K, Takano S, Iwase D, Aikawa J, Inoue G, Miyagi M, Takaso M
    • Journal Title

      Lipid in health and disease

      Volume: 17 Issue: 1 Pages: 137-137

    • DOI

      10.1186/s12944-018-0792-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 変形性膝関節症患者の滑膜組織におけるPeptide Lvの発現と疼痛への関与の検討.2020

    • Author(s)
      迎 学、内田健太郎、高野昇太郎、高田 研、岩瀬 大、相川 淳、大貫裕子、関口裕之、井上 玄、高相晶士
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 女性の変形性膝関節症患者の滑膜組織では男性に比べカルシトニン遺伝子関連ペプチド受容体RAMP1の発現が高い2020

    • Author(s)
      内田健太郎、高野昇太郎、高田 研、迎 学、相川 淳、岩瀬 大、井上 玄、高相晶士
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 滑膜線維芽細胞における古典経路と非古典経路のクロストークを介したTGF-βによるVEGF制御機構2019

    • Author(s)
      高野昇太郎、内田健太郎、庄司真太郎、相川淳、岩瀬大、迎学、宮城正行、関口裕之、大貫裕子、高相晶士
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Transforming Growth Factor-beta Stimulates Nerve Growth Factor Production Via The Tak1/p38 Pathway In Osteoarthritic Synovium.2019

    • Author(s)
      Kawakubo A, Uchida K, Takano S, Aikawa J, Iwase D, Miyagi M, Nakawaki M, Sekiguchi H, Inoue G, Takaso M.
    • Organizer
      ORS 2019 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肥満を有する変形性膝関節症患者の滑膜組織におけるMast cellの増加2018

    • Author(s)
      内田健太郎、高野昇太郎、岩瀬大、相川淳、迎 学、井上 玄、宮城正行、小沼賢治、齋藤 亘、高相晶士.
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト滑膜組織におけるC型レクチン受容体 macrophage inducible C-type leptin の発現とその制御機構の検討2018

    • Author(s)
      森谷光俊、内田健太郎、高野昇太郎、岩瀬 大、井上 玄、宮城正行、田澤諒、中脇充章、大貫裕子、高相晶士
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] HbA1c高値の変形性膝関節症患者の膝蓋下脂肪体ではTNF-alpha, IL-8が亢進している2018

    • Author(s)
      迎 学、内田健太郎、高野昇太郎、相川淳、岩瀬大、宮城正行、東山礼治、井上 玄、大貫裕子、高相晶士
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 血管内皮増殖因子は変形性膝関節症患者の非炎症性疼痛に関与する2018

    • Author(s)
      高野昇太郎、内田健太郎、迎 学、岩瀬 大、相川 淳、村田幸佑、宮城正行、井上 玄、大貫裕子、高相晶士
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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