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Anti-VEGF therapy for osteoarthritis and the related pain

Research Project

Project/Area Number 16K20068
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionJuntendo University

Principal Investigator

Nagao Masashi  順天堂大学, 革新的医療技術開発研究センター, 講師 (50384110)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords変形性膝関節症 / 血管因子増殖因子 / 軟骨代謝 / 血管内皮増殖因子 / 変形性関節症 / 臨床 / 治療
Outline of Final Research Achievements

Previous study indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA). In this study, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症(OA)は関節軟骨の変性と摩耗を経て、関節の変形をきたす疾患である。様々なOA発症の分子機構への理解が深まっているが、現在用いられる薬剤は消炎鎮痛を目的とするものであり、OA進行の抑制あるいは改善をもたらす治療薬の開発が期待されている。本研究を通じて、マウスモデルにおいて、VEGFは膝OAの進行に促進的に働き、抗VEGFの抗体やVEGF阻害薬の投与により膝OAの進行を抑制することが可能であった。今後ヒトにおける膝OAの治療法の候補となりえると考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (32 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Int'l Joint Research] ハーバード大学歯学部(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Harvard School of Dental Medicine/Rush University(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Harvard School of Dental Medicine/Rush Unicersity(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] 変形性膝関節症における血管内皮増殖因子VEGFの役割2019

    • Author(s)
      長尾雅史
    • Journal Title

      Journal of Musculoskeletal Pain Research

      Volume: 11 Pages: 2186-2796

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Biomechanical evaluation of a transcondylar screw from the dorsolateral plate support on the stabilization of orthogonal plate configuration in distal humeral fracture2019

    • Author(s)
      Hara Akira、Kudo Toshiya、Ichihara Satoshi、Iwase Hideaki、Nagao Masashi、Maruyama Yuichiro、Kaneko Kazuo
    • Journal Title

      Injury

      Volume: 50 Issue: 2 Pages: 256-262

    • DOI

      10.1016/j.injury.2018.12.017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Playing football on artificial turf as a risk factor for fifth metatarsal stress fracture: a retrospective cohort study2019

    • Author(s)
      Miyamori Takayuki、Nagao Masashi、Sawa Ryuichi、Tumilty Steve、Yoshimura Masafumi、Saita Yoshitomo、Ikeda Hiroshi、Kaneko Kazuo
    • Journal Title

      BMJ Open

      Volume: 9 Issue: 2 Pages: e022864-e022864

    • DOI

      10.1136/bmjopen-2018-022864

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High incidence of posterior glenoid dysplasia of the shoulder in young baseball players2019

    • Author(s)
      Kirimura Kengo、Nagao Masashi、Sugiyama Masahiro
    • Journal Title

      Journal of Shoulder and Elbow Surgery

      Volume: 28 Issue: 1 Pages: 82-87

    • DOI

      10.1016/j.jse.2018.06.021

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Knee hyperextension and a small lateral condyle are associated with greater quantified antero-lateral rotatory instability in the patients with a complete anterior cruciate ligament (ACL) rupture2018

    • Author(s)
      Saita Yoshitomo、Schoenhuber Herbert、Thi?bat Gabriele、Ravasio Giovanni、Pozzoni Roberto、Panzeri Andrea、Galli Marco、Nagao Masashi、Takazawa Yuji、Ikeda Hiroshi、Kaneko Kazuo
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: 27 Issue: 3 Pages: 868-874

    • DOI

      10.1007/s00167-018-5143-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 臨床研究法の施行と再生医療等安全性確保法施行規則改正に関して2018

    • Author(s)
      本間 康弘, 岩崎 昭夫, 長尾 雅史, 平野 景子, 飛田 護邦, 西崎 祐史, 藤林 和俊, 眞野 訓, 奥澤 淳司
    • Journal Title

      再生医療

      Volume: 17 Pages: 326-332

    • NAID

      40021675185

    • Related Report
      2018 Research-status Report
  • [Journal Article] 骨粗鬆症がもたらす脊椎関連の痛み2018

    • Author(s)
      野尻 英俊, 石島 旨章, 長尾 雅史, 奥田 貴俊, 金子 和夫
    • Journal Title

      ペインクリニック

      Volume: 40 Pages: 239-244

    • Related Report
      2018 Research-status Report
  • [Journal Article] 変形性膝関節症の運動療法 その意義と実際2018

    • Author(s)
      石島 旨章, 金子 晴香, 清村 幸雄, 劉 立足, 有田 均, 羽田 晋之介, 青木 孝子, 西尾 啓史, 塩澤 淳, 根岸 義文, 百枝 雅裕, 長尾 雅史, 永山 正隆, 斎田 良知, 高澤 祐治, 池田 浩, 岡田 保典, 黒澤 尚, 金子 和夫
    • Journal Title

      ペインクリニック

      Volume: 17 Pages: 326-332

    • Related Report
      2018 Research-status Report
  • [Journal Article] スポーツ傷害の予防・診断・治療】 スポーツ障害予防 第5中足骨疲労骨折(Jones骨折)の予防2018

    • Author(s)
      齋田 良知, 池田 浩, 小林 洋平, 長尾 雅史, 小林 慶司, 金子 和夫
    • Journal Title

      別冊整形外科

      Volume: 73 Pages: 1215-1228

    • Related Report
      2018 Research-status Report
  • [Journal Article] 【変形性膝関節症の早期病変の診断から治療まで】 早期OAの病態 早期膝OAの臨床病態 軟骨成分を加味した骨棘と半月板逸脱の関連2018

    • Author(s)
      石島 旨章, 羽田 晋之介, 金子 晴香, 劉 立足, 青木 孝子, 根岸 義文, 百枝 雅裕, 久保田 光昭, 長尾 雅史, 斎田 良知, 高澤 祐治, 池田 浩, 岡田 保典, 金子 和夫
    • Journal Title

      THE BONE

      Volume: 32 Pages: 45-53

    • Related Report
      2018 Research-status Report
  • [Journal Article] Prediction Model of In-Hospital Mortality After Hip Fracture Surgery2018

    • Author(s)
      Endo Atsushi、Baer Heather J.、Nagao Masashi、Weaver Michael J.
    • Journal Title

      Journal of Orthopaedic Trauma

      Volume: 32 Issue: 1 Pages: 34-38

    • DOI

      10.1097/bot.0000000000001026

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis2018

    • Author(s)
      Kinoshita Mayuko、Ishijima Muneaki、Kaneko Haruka、Liu Lizu、Nagao Masashi、Sadatsuki Ryo、Hada Shinnosuke、Arita Hitoshi、Aoki Takako、Yamanaka Makoto、Nojiri Hidetoshi、Sakamoto Yuko、Tokita Akifumi、Kaneko Kazuo
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 1 Pages: 1-8

    • DOI

      10.1080/14397595.2018.1442671

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis2017

    • Author(s)
      Nagao Masashi、Hamilton John L.、Kc Ranjan、Berendsen Agnes D.、Duan Xuchen、Cheong Chan Wook、Li Xin、Im Hee-Jeong、Olsen Bjorn R.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 13027-13027

    • DOI

      10.1038/s41598-017-13417-w

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Range limitation in hip internal rotation and fifth metatarsal stress fractures (Jones fracture) in professional football players2017

    • Author(s)
      Saita Yoshitomo、Nagao Masashi、Kawasaki Takayuki、Kobayashi Yohei、Kobayashi Keiji、Nakajima Hiroki、Takazawa Yuji、Kaneko Kazuo、Ikeda Hiroshi
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: - Issue: 7 Pages: 1943-1949

    • DOI

      10.1007/s00167-017-4552-4

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Physical activity for knee osteoarthritis.2017

    • Author(s)
      Nagao M, Ishijima M, Kaneko H, Takazawa Y, Ikeda H, Kaneko K.
    • Journal Title

      Clin Calcium

      Volume: 1 Pages: 25-30

    • Related Report
      2016 Research-status Report
  • [Journal Article] Biomechanical properties of orthogonal plate configuration versus parallel plate configuration using the same locking plate system for intra-articular distal humeral fractures under radial or ulnar column axial load.2016

    • Author(s)
      Kudo T, Hara A, Iwase H, Ichihara S, Nagao M, Maruyama Y, Kaneko K.
    • Journal Title

      Injury

      Volume: 10 Issue: 10 Pages: 2071-2076

    • DOI

      10.1016/j.injury.2016.08.012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain2016

    • Author(s)
      Hamilton JL, Nagao M, Levine BR, Chen D, Olsen BR, Im HJ
    • Journal Title

      J Bone Miner Res

      Volume: 5 Issue: 5 Pages: 911-924

    • DOI

      10.1002/jbmr.2828

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Leukocyte concentration and composition in platelet-rich plasma (PRP) influences the growth factor and protease concentrations2016

    • Author(s)
      Yohei Kobayashi, Yoshitomo Saita, Hirofumi Nishio, Hiroshi Ikeda, Yuji Takazawa, Masashi Nagao, Tomoiku Takaku, Norio Komatsu, Kazuo Kaneko
    • Journal Title

      Journal of orthopaedic science

      Volume: 21 Issue: 5 Pages: 683-689

    • DOI

      10.1016/j.jos.2016.07.009

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 変形性膝関節症の疼痛と関連する病態2016

    • Author(s)
      石島 旨章(順天堂大学 大学院医学研究科整形外科・運動器医学), 金子 晴香, 羽田 晋之介, 劉 立足, アヌワル・ジャン・ユユプ , 清村 幸雄, 木下 真由子, 有田 均, 塩澤 淳, 青木 孝子, 長尾 雅史, 高澤 祐治, 池田 浩, 岡田 保典, 金子 和夫
    • Journal Title

      リウマチ科

      Volume: 56 Pages: 632-640

    • Related Report
      2016 Research-status Report
  • [Presentation] 骨粗鬆症治療におけるtreat-to-target(T to T) 骨粗鬆症治療におけるtreat-to-target 骨吸収抑制剤(BP製剤)の視点から2018

    • Author(s)
      長尾 雅史, 石島 旨章, 木下 真由子, 金子 和夫
    • Organizer
      関東整形災害外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 変形性膝関節症における血管内皮間葉分化転換(EndMT)の関与について2017

    • Author(s)
      長尾雅史 他
    • Organizer
      日本整形外科学会 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 変形性関節症における血管内皮増殖因子VEGFの役割2017

    • Author(s)
      長尾雅史
    • Organizer
      日本関節病学会 2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 軟骨発生および変形性関節症における異なる血管内皮増殖因子の役割2017

    • Author(s)
      長尾雅史
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] サッカー選手における人工芝使用による第5中足骨疲労骨折リスク推定2017

    • Author(s)
      長尾雅史
    • Organizer
      日本関節鏡・膝・スポーツ整形外科学会 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] サッカー選手における第5中足骨疲労骨折の危険因子としての人工芝のリスク推定2017

    • Author(s)
      長尾雅史
    • Organizer
      日本整形外科スポーツ医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 第五中足骨疲労骨折の撲滅への取り組み2016

    • Author(s)
      長尾雅史
    • Organizer
      第5回JJ会合同力ンファレンス
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2016-11-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 変形性膝関節症と血管内皮増殖因子VEGF2016

    • Author(s)
      長尾雅史、Bjron Olsen、Hee-Jeong Im
    • Organizer
      Orthopedic Research Club
    • Place of Presentation
      かずさアカデミアパーク
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 軟骨発生と変形性関節症における血管内皮増殖因子(VEGF)の役割2016

    • Author(s)
      長尾雅史、Bjron Olsen
    • Organizer
      日本整形外科基礎学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] Lower limb alignment as an important factor for managing atypical fracture2016

    • Author(s)
      長尾雅史、斎田良知、石島旨章、金子和夫
    • Organizer
      日本骨代謝学会、アジア太平洋骨代謝学会議
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-07-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2022-02-21  

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