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2007 Fiscal Year Final Research Report Summary

Analysis of Wnt Signaling in Chondrogenic Differentiation for Osteoarthritis

Research Project

Project/Area Number 18591655
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

MIURA Toshiki  The University of Tokyo, Faculty of Medicine, Assistant Professor (20376479)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA Shuichi  The University of Tokyo, Faculty of Medicine, Assistant Professor (80401066)
HARA Nobuhiro  The University of Tokyo, Faculty of Medicine, Assistant Professor (00422296)
OGATA Naoshi  The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor (10361495)
KAWANO Hirotaka  The University of Tokyo, Faculty of Medicine, Lecturer (20345218)
Project Period (FY) 2006 – 2007
KeywordsOsteoarthritis / Canonical Wnt signaling / TCF / LEF-1 / Hypertrophy / Sox9
Research Abstract

To better understand the role of the canonical Wnt signaling pathway in cartilage development and Osteoarthritis (OA) condition, we adenovirally expressed a constitutively active (ca) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effecter of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of β-catenin suppressed LiCl promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type but not in Sox9-deficient cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. Next, In vivo experiment, mouse OA model was created by surgical transection of the medial collateral ligament and resection of the medial meniscus of the knee joints of wild-type. Cartilage destruction and osteophyte formation in the medial tibial cartilage were compared by histologic and radiographic analyses. Expression of type X collagen, TCF/LEF-1 and β-catenin was examined by immunohistochemistry. TCF/LEF-1 was induced in the articular cartilage of wild-type mice at the early stage of OA, almost simultaneously with type X collagen as compared with wild-type mice. These in vivo results perform similar functions with that RUNX-2 contributes to the pathogenesis of OA through chondrocyte hypertrophy and matrixbreakdown after the induction of joint instability (Our group published).

  • Research Products

    (15 results)

All 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Continuous activation of Gαq in osteoblasts results in osteopenia through impaired osteoblast differentiation.2007

    • Author(s)
      Naoshi Ogata, et. al.
    • Journal Title

      J Biol Chem 282

      Pages: 35757-64

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Akt1 in osteoblasts and osteoclasts controls bone remode ling2007

    • Author(s)
      Naohiro Kawamura, et. al.
    • Journal Title

      PLoS ONE 2

      Pages: 1058

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Akt1 in osteoblasts and osteoclasts controls bone remodeling2007

    • Author(s)
      Kawamura N, Kugimiya F, Oshima Y, Ohba S, Ikeda T, Saito T, Shinoda Y, Kawasaki Y, Ogata N, Hoshi K, Akiyama T, Tobe T, Kadowaki T, Azuma Y, Tanaka S, Nakamura K, Chung UI, and Kawaguchi H
    • Journal Title

      PLoS ONE 2(10)

      Pages: e1058

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation2007

    • Author(s)
      Ogata N, Kawaguchi H, Chung UI, Roth SI, Segre GV.
    • Journal Title

      J Biol Chem 282

      Pages: 35757-64

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification2006

    • Author(s)
      Takashi Yamada, et. al.
    • Journal Title

      Nat Medicine 12: 665-670, 2006 12

      Pages: 665-670

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neurologic level diagnosis of cervical stenotic myeiopathy2006

    • Author(s)
      Seichi A, Takeshita K, Kawaguchi H, Matsudaira K, Higashikawa A, Ogata N, Nakamura K
    • Journal Title

      Spine 31

      Pages: 1338-1343

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification2006

    • Author(s)
      Yamada T, Kawano H, Koshizuka Y, Fukuda T, Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung UI, Nakamura K, Kato S, Kawaguchi H
    • Journal Title

      Nat Med 12

      Pages: 665-670

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways2006

    • Author(s)
      Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI, Nakamura K, Kawaguchi H.
    • Journal Title

      J Cell Biochem 99(1)

      Pages: 196-208

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Gαq signaling in osteoblasts inhibits bone formation2007

    • Author(s)
      Ogata N, Shinoda Y, Yano F, Wettschureck N, Offermanns S, Segre GV, Nakamura K, Kawaguchi H
    • Organizer
      29th annual meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      20070916-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Runxl, co-activator of Sox5, Sox6 and Sox9(the Sox trio) regulates chondrogenic differentiation2007

    • Author(s)
      Yano F, Ikeda T, Saito T, Ogata N, Takeda S, Kimura A, Ohba S, Kugimiya F, Nakamura K, Takato T, Kawaguchi H and Chung U.
    • Organizer
      29th annual meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      20070916-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Fluoroscopic Navigation Assisted ACL Reconstruction2007

    • Author(s)
      Nakayama S, Nakagawa T, Fukai At, Nakajima K, Nakamura K
    • Organizer
      ISAKOS Biennial Congress
    • Place of Presentation
      Florence
    • Year and Date
      20070527-31
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Biodissociatable phospholipids polymaer hydrogel prevents tendon adhesion without impairing healing2007

    • Author(s)
      Ishiyama N, Moro T, Ohe T, Miura T, Ishihara K, Konno T, Kimura M, Nakamura K and Kawaguchi H
    • Organizer
      53rd Annual Meeting of the Orthopaedic Research Society(ORS)
    • Place of Presentation
      San Diego, USA
    • Year and Date
      20070211-13
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Gaq Signaling in Osteoblasts Inhibits Bone Formation2007

    • Author(s)
      Naoshi Ogata
    • Organizer
      The American Society for Bone and Mineral Reserch
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2007-09-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Correction of scoliosis using segmental pedicle screw instrumentation versus hybrid constructs with hooks and screws2006

    • Author(s)
      Takeshita K, Maruyama T, Murakami M, Higashikawa A, Hashimoto H, Hara N, Seichi A, Nakamura K
    • Organizer
      6th Biennial Meeting of the International Society of Spinal Deformities
    • Place of Presentation
      Gent, Belgium
    • Year and Date
      20060621-24
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] CLINICAL CALCIUM 副甲状腺ホルモンの骨形成促進作用のメカニズム2007

    • Author(s)
      緒方直史
    • Total Pages
      10
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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