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Identification of candidate compounds for the maintenance of SFZ in the articular cartilage through Prg4 induction

Research Project

Project/Area Number 15K15536
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

Yano Fumiko  東京大学, 医学部附属病院, 特任講師 (80529040)

Co-Investigator(Kenkyū-buntansha) 小林 寛  東京大学, 医学部附属病院, その他 (20407951)
森崎 裕  東京大学, 医学部附属病院, 助教 (30508099)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords変形性膝関節症 / 関節軟骨最表層 / ルブリシン / 低分子化合物
Outline of Final Research Achievements

The superficial zone (SFZ) of articular cartilage plays a cartilage-protective role by secretion of lubricin (Prg4). We separately isolated the SFZ cells and then treated with various agonists which are related to chondrogenic differentiation. When we analyzed treated SFZ cells by RT-PCR, Hif2a and Wnt signaling are candidate for upregulation of Prg4 expression and were performed by cDNA microarray. Since Hif2a significantly showed Prg4-promoter activity, to further know the mechanism of Prg4 regulation by Hif2a, we performed ChIP sequencing analysis using activated Hif2a in SFZ cells. In vivo analysis, we analyzed OA development of 4 types; Prg4-CreERT2; Hif2a flox (loss-of-function) or Hif2a Tg mice (activated Hif2a in Prg4 expressing cells), Prg4-CreERt2; βcatenin flox mice (loss-of-function) or Prg4-CreERt2; βcateninEx3 flox (activated βcatenin in Prg4 expressing cells).

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (34 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (17 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 17 results,  Open Access: 12 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (3 results)

  • [Int'l Joint Research] Boston Children's Hospital/Orthopedics surgery/Harvard Medical School(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology.2018

    • Author(s)
      Fujii Y, Kawase-Koga Y, Hojo H, Yano F, Sato M, Chung UI, Ohba S, Chikazu D.
    • Journal Title

      Stem Cell Res Ther

      Volume: 9 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s13287-018-0783-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Mouse Intervertebral Disc Degeneration Model by Surgically-Induced Instability2017

    • Author(s)
      Oichi T, Taniguchi Y, Soma K, Chang SH, Yano F, Tanaka S, Saito T
    • Journal Title

      Spine

      Volume: ― Issue: 10 Pages: 1-1

    • DOI

      10.1097/brs.0000000000002427

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lymphaticovenous anastomoses for lymphedema complicated by severe lymphorrhea following resection of soft-tissue sarcomas of the adductor compartment: A report of two cases2017

    • Author(s)
      Kobayashi H, Iida T, Yamamoto T, Ikegami M, Shinoda Y, Tanaka S, Kawano H.
    • Journal Title

      JBJS Case Connect

      Volume: 7 Issue: 4 Pages: e80-e80

    • DOI

      10.2106/jbjs.cc.17.00078

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and clinical outcomes of hip fractures and subchondral insufficiency fractures of the femoral head in patients with tumour-induced osteomalacia2017

    • Author(s)
      Kobayashi Hiroshi、Ito Nobuaki、Akiyama Toru、Okuma Tomotake、Kinoshita Yuka、Ikegami Masachika、Shinoda Yusuke、Fukumoto Seiji、Tanaka Sakae、Kawano Hirotaka
    • Journal Title

      International Orthopaedics

      Volume: 41 Issue: 12 Pages: 2597

    • DOI

      10.1007/s00264-017-3610-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple Acrometastases in a Patient with Renal Pelvic Urothelial Cancer2017

    • Author(s)
      Sawada Ryoko、Shinoda Yusuke、Niimi Aya、Nakagawa Tohru、Ikegami Masachika、Kobayashi Hiroshi、Tanaka Sakae、Homma Yukio、Haga Nobuhiko
    • Journal Title

      Case Reports in Urology

      Volume: 2017 Pages: 1-4

    • DOI

      10.1155/2017/7830207

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anterior Impingement Syndrome of the Ankle Caused by Osteoid Osteoma in the Talar Neck Treated with Arthroscopy and 3D C-Arm-Based Imaging2017

    • Author(s)
      Masachika Ikegami, Takumi Matsumoto, Song Ho Chang, Hiroshi Kobayashi, Yusuke Shinoda, and Sakae Tanaka
    • Journal Title

      Case Reports in Orthopedics

      Volume: 2017 Pages: 2171627-2171627

    • DOI

      10.1155/2017/2171627

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional fluoroscopic navigation-assisted surgery for tumors in patients with tumor-induced osteomalacia in the bones2017

    • Author(s)
      Kobayashi H, Akiyama T, Okuma T, Shinoda Y, Oka H, Ito N, Fukumoto S, Tanaka S, Kawano H.
    • Journal Title

      Comput Assist Surg

      Volume: 22 Issue: 1 Pages: 14

    • DOI

      10.1080/24699322.2017.1282044

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different regulation of limb development by p63 transcript variants2017

    • Author(s)
      Kawata M, Taniguchi Y, Mori D, Yano F, Ohba S, Chung UI, Shimogori T, Mills AA, Tanaka S, Saito T
    • Journal Title

      PLoS One

      Volume: 12 Issue: 3 Pages: e0174122-e0174122

    • DOI

      10.1371/journal.pone.0174122

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.2017

    • Author(s)
      Taniguchi Y, Kawata M, Chang SH, Mori D, Okada K, Kobayashi H, Sugita S, Hosaka Y, Inui H, Taketomi S, Yano F, Ikeda T, Akiyama H, Mills AA, Chung UI, Tanaka S, Kawaguchi H, and Saito T*
    • Journal Title

      Arthritis Rheumatol.

      Volume: 69 Issue: 3 Pages: 598-609

    • DOI

      10.1002/art.39976

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma2017

    • Author(s)
      Tsuda Y, Ogura K, Kobayashi E, Hiruma T, Iwata S, Asano N, Kawai A, Chuman H, Ishii T, Morioka H, Kobayashi H, Kawano H.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 47 Issue: 5 Pages: 422

    • DOI

      10.1093/jjco/hyx016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes.2016

    • Author(s)
      Kobayashi H, Chang S, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung U, Akiyama H, Kawaguchi H, Tanaka S, Saito T.
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 13336-13336

    • DOI

      10.1038/ncomms13336

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability2016

    • Author(s)
      Chang SH, Yasui T, Taketomi S, Matsumoto T, Kim-Kaneyama JR, Omiya T, Hosaka Y, Inui H, Omata Y, Yamagami R, Mori D, Yano F, Chung U, Tanaka S, Saito T.
    • Journal Title

      Osteoarthritis Cartilage

      Volume: 24 Issue: 4 Pages: 688

    • DOI

      10.1016/j.joca.2015.11.008

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Grey-scale sonography and sonoelastography for diagnosing carpal tunnel syndrome.2016

    • Author(s)
      Miyamoto H, Morizaki Y, Kashiyama T, Tanaka S.
    • Journal Title

      World J Radiol.

      Volume: 8 Issue: 3 Pages: 281-7

    • DOI

      10.4329/wjr.v8.i3.281

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study.2016

    • Author(s)
      Kodama R, Muraki S, Oka H, Iidaka T, Teraguchi M, Kagotani R, Asai Y, Yoshida M, Morizaki Y, Tanaka S, Kawaguchi H, Nakamura K, Akune T, Yoshimura N
    • Journal Title

      Mod Rheumatol.

      Volume: 16 Pages: 1-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b>2015

    • Author(s)
      Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
    • Journal Title

      Biomedical Research

      Volume: 36 Issue: 3 Pages: 179-186

    • DOI

      10.2220/biomedres.36.179

    • NAID

      130005083858

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Runx1 and Runx3 Are Downstream Effectors of Nanog in Promoting Osteogenic Differentiation of the Mouse Mesenchymal Cell Line C3H10T1/22015

    • Author(s)
      Saito T, Ohba S, Yano F, Seto I, Yonehara Y, Takato T, Ogasawara T
    • Journal Title

      Cell Reprogram

      Volume: 17 Issue: 3 Pages: 227-234

    • DOI

      10.1089/cell.2014.0059

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding pr</b><b>oteins </b>2015

    • Author(s)
      Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung UI, Tanaka S, Saito T
    • Journal Title

      Biomedical Research

      Volume: 36 Issue: 1 Pages: 21-29

    • DOI

      10.2220/biomedres.36.21

    • NAID

      130004903876

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] β-cateninシグナルは関節軟骨最表層の維持に必須である2017

    • Author(s)
      玄 峰俊、矢野 文子、斎藤 琢
    • Organizer
      第35回日本骨代謝学会、第32回日本整形外科学会基礎、第31回日本軟骨代謝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 関節軟骨最表層に発現する転写因子 HIF-2α は,関節軟骨の維持に不可欠である2017

    • Author(s)
      牧井 勇磨、矢野 文子、斎藤 琢
    • Organizer
      第35回日本骨代謝学会、第32回日本整形外科学会基礎
    • Related Report
      2017 Annual Research Report
  • [Presentation] Runx1 contributes to articular cartilage maintenance through enhancement of cartilage matrix production and suppression of hypertrophic differentiation2016

    • Author(s)
      Fumiko Yano, Taku Saito, Shinsuke Ohba, Sakae Tanaka, Ung-il Chung
    • Organizer
      Cold Spring Harbor Asia conference on Bone & Cartilage: From Development to Human Diseases
    • Place of Presentation
      The Suzhou Dushu Lake Conference Center
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      第31回日本整形外科学会基礎学術集会
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡・福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子
    • Organizer
      第34回日本骨代謝学会学術集会 / 第3回アジア太平洋骨代謝学会議
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-07-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子、斎藤琢、大庭伸介、田中栄、鄭雄一
    • Organizer
      第2回 骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄スパ&リゾート
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Runx1による軟骨分化制御機構2016

    • Author(s)
      矢野文子
    • Organizer
      第2回日本骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄スパ&リゾート(沖縄・恩納村)
    • Year and Date
      2016-07-06
    • Related Report
      2015 Research-status Report
  • [Presentation] Runx1 contributes to articular cartilage maintenance through enhancement of cartilage matrix production and suppression of hypertrophic differentiation2016

    • Author(s)
      Fumiko Yano, Taku Saito, Shinsuke Ohba, Ung-il Chung
    • Organizer
      The second Herbert Fleisch Workshop
    • Place of Presentation
      Novotel Brugge Centrum (Belgium・Brugge)
    • Year and Date
      2016-02-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 軟骨再生を誘導する変形関節症治療候補薬のin vivoモデルにおける効果~そのメカにニズムの解析とターゲット分子の探索~2015

    • Author(s)
      矢野文子
    • Organizer
      第18回骨代謝研究会
    • Place of Presentation
      慶応義塾大学医学部総合医科学研究棟(東京・新宿区)
    • Year and Date
      2015-11-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] A novel disease-modifying osteoarthritis drug candidate targeting Runx12015

    • Author(s)
      Fumiko Yano
    • Organizer
      LMU-Utokyo Symposium
    • Place of Presentation
      Innnovation Center for Biotechnology (Germany・Munich)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Runx1による軟骨分化制御機構2015

    • Author(s)
      矢野文子
    • Organizer
      第16回運動器科学研究会
    • Place of Presentation
      みなみホール(鹿児島県・鹿児島市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Remarks] 東京大学 工学系研究科/医学系研究科 鄭雄一研究室

    • URL

      http://www.tetrapod.t.u-tokyo.ac.jp/med/index.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 東京大学医学部附属病院 顎口腔外科・歯科矯正歯科

    • URL

      http://plaza.umin.ac.jp/~oralsurg/

    • Related Report
      2015 Research-status Report
  • [Remarks] 東京大学医学部附属病院 整形外科・脊椎外科

    • URL

      http://www.u-tokyo-ortho.jp/about/achievements/achievements.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-06-07  

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