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2006 Fiscal Year Final Research Report Summary

Regulation of osteoclastogenesis by a novel surface membrane receptor-like molecule : Preparation of gene-deficient mice and molecular histological analysis

Research Project

Project/Area Number 16390528
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KUKITA Toshio  Kyushu University, Faculty of Dental Science, Professor, 歯学研究院, 教授 (70150464)

Co-Investigator(Kenkyū-buntansha) KUKITA Akiko  Saga University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30153266)
NAGATA Kengo  Kyushu University, Faculty of Dental Science, Research Associate, 歯学研究院, 助手 (90189134)
Project Period (FY) 2004 – 2006
Keywordsosteoclast / differentiation / DC-STAMP / fusion / membrane protein with 7 transmembrane domains
Research Abstract

We have firstly developed the cell line to research the fusion mechanism of mononuclear pre-osteoclasts. RAW-D clone, a subclone of murine macrophage-like RAW264 cells, is the most suitable clone highly sensitive to RANKL to differentiate into osteoclasts. As the 2nd step, we have searched gene specifically expressed in RAW-D cells after stimulation with RANKL by use of RNA subtraction techniques. For the 3rd step, we have evaluated the function of obtained genes. We have cloned genome of DC-STAMP from appropriate BAC clone and constructed the targeting vector followed by introducing the vector into ES cells. However, we could not obtain stable ES cells targeted DC-STAMP gene. We have modified the design of the targeting vector and introduced it into ES cells. Now we are trying the efforts to obtain stable ES clone. On the other hand, we have evaluated the function of DC-STAMP in osteoclastogenesis by use of several in vitro cell culture systems. We have transfected RAW-D cells with fu … More ll length cDNA for DC-STAMP and ΔT7 DC-STAMP ligated into the expression vector pCIneo. Both of these cDNA construct significantly augmented osteoclastogenesis induced by RANKL. As DC-STAMP and ΔT7 DC-STAMP significantly stimulated formation of osteoclasts with numerous nuclei, it was estimated that DC-STAMP has pivotal roles in the fusion among pre-osteoclasts. By the way, we have ligated DC-STAMP and AT7 DC-STAMP into pEGFPN1 to prepare GFP-fusion protein at C-terminus of these molecules. When we transfected these constructs into RAW-D cells, to our surprise, a significant induction of TRAP-positive cells (also induced TRAP-positive multinucleated cell) was observed. Even in the absence of RANKL. These data suggest a presence of regulatory domain at the C-terminal portion of DC-STAMP. Loss-of-function studies by use of specific siRNA clearly showed a marked inhibition of osteoclastogenesis involving multinucleation process. It is now elucidated that DC-STAMP is a key regulatory molecule in osteoclastogenesis especially in fusion process of pre-osteoclasts. Our findings would open a new aspect of therapeutic way to regulate inflammatory bone destruction. Less

  • Research Products

    (18 results)

All 2007 2006 2005 2004

All Journal Article (18 results)

  • [Journal Article] Adiponectin inhibits osteoclast formation stimuloated by lipopolysaccharide from Actinobacillus acitinomycetemcomitans.2007

    • Author(s)
      Yamaguchi N., Kukita T., Li Y-J., Arguesta J.G.M., Saito T., Hanazawa S., Yamashita Y.
    • Journal Title

      FEMS Immunology & Microbiology 49

      Pages: 28-34

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds : successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.2006

    • Author(s)
      Tang Q-Y., Kukita T., Ushijima Y., Kukita A., Nagata K., Sandra F., Watanabe T., Toh K., Okuma Y., Kawasaki S., Rasubala L., Teramachi J., Miyamoto I., Wu Z., Iijima T.
    • Journal Title

      Histochem. Cell Biol. 125

      Pages: 215-225

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The contribution of platelet-derived growth factor, transforming growth factor-<beta>1 and insulin-like growth factor-I in platelet-rich plasma (PRP) to the proliferation of osteoclast-like cells.2006

    • Author(s)
      Ogino Y., Ayukawa Y., Kukita T., Koyano K.
    • Journal Title

      Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 101

      Pages: 724-729

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds : successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.2006

    • Author(s)
      Tang Q-Y., Kukita T., Ushijima Y., Kukita A., Nagata K., Sandra F., Watanabe T., Toh K., Okuma Y., Kawasaki S., Rasubala L., Teramachi J., Miyamoto I., Wu Z., Iijima T.
    • Journal Title

      Histochem.Cell Biol. 125

      Pages: 215-225

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of Histone Deacetylase Suppresses Osteoclastogenesis and Bone Destruction by Inducing IFN-{beta} Production.2005

    • Author(s)
      Nakamura T., Kukita T., Shobuike T., Nagata K., Wu Z., Ogawa K., Hotokebuchi T., Kohashi O., Kukita A.
    • Journal Title

      J. Immunol. 175

      Pages: 5809-5816

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of genes differentially expressed in osteoclast-like cells.2005

    • Author(s)
      Nomiyama H., Egami K., Wada N., Toh K., Horiuchi M., Matsusaki H., Miura R., Yoshie O., Kukita T.
    • Journal Title

      J. Interferon Cytokine Res. 25

      Pages: 227-231

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppressors of cytokine signaling-1 and -3 regulate osteoclastogenesis in the presence of inflammatory cytokines.2005

    • Author(s)
      Ohishi M., Matsumura Y., Aki D., Mashima R., Taniguchi K., Kobayashi T., Kukita T., Iwamoto Y., Yoshimura A.
    • Journal Title

      J. Immunol. 174

      Pages: 3024-3031

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of Histone Deacetylase Suppresses Osteoclastogenesis and Bone Destruction by Inducing IFN-{beta} Production.2005

    • Author(s)
      Nakamura T., Kukita T., Shobuike T., Nagata K., Wu Z., Ogawa K., Hotokebuchi T., Kohashi O., Kukita T.
    • Journal Title

      J.Immunol. 175

      Pages: 5809-5816

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ameloblastoma induces osteoclastogenesis : a possible role of ameloblastoma in expanding in the bone.2005

    • Author(s)
      Sandra F., Hendarmin L., Kukita T., Nakao Y., Nakamura N., Nakamura S.
    • Journal Title

      Oral Oncol. 41

      Pages: 637-644

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of genes differentially expressed in osteoclast-like cells.2005

    • Author(s)
      Nomiyama H., Egami K., Wada N., Toh K., Horiuchi M., Matsusaki H., Miura R., Yoshie O., Kukita T.
    • Journal Title

      J.Interferon Cytokine Res. 25

      Pages: 227-231

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Suppressors of cytokine signaling-1 and-3 regulate osteoclastogenesis in the presence of inflammatory cytokines.2005

    • Author(s)
      Ohishi M., Matsumura Y., Aki D., Mashima R., Taniguchi K., Kobayashi T., Kukita T., Iwamoto Y., Yoshimura A.
    • Journal Title

      J.Immunol. 174

      Pages: 3024-3031

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] RANKL-induced DC-STAMP is essential for osteoclastogenesis.2004

    • Author(s)
      Kukita T., Wada N., Kukita A., Karkimoto T., Sandra F., Toh K., Nagata K., Iijima T., Horiuchi M., Matsusaki H., Hieshima K., Yoshie O., Nomiyama H.
    • Journal Title

      J. Exp. Med. 200

      Pages: 941-946

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible involvement of MIP-1alpha in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis.2004

    • Author(s)
      Toh K., Kukita T., Wu Z., Kukita A., Sandra F., Tang Q-Y., Nomiyama H., Iijima T.
    • Journal Title

      Lab. Invest. 84

      Pages: 1092-1102

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RANKL-induced DC-STAMP is essential for osteoclastogenesis.2004

    • Author(s)
      Kukita T., Wada N., Kukita A., Kakimoto T., Sandra F., Toh K., Nagata K., Iijima T., Horiuchi M., Matsusaki H., Hieshima K., Yoshie O., Nomiyama H.
    • Journal Title

      J.Exp.Med. 200

      Pages: 941-946

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation.2004

    • Author(s)
      Ikeda F., Nishimura R., Matsubara T., Tanaka S., Inoue J., Reddy S.V., Hata K., Yamashita K., Hiraga T., Watanabe T., Kukita T., Yoshioka K., Rao A., Yoneda T.
    • Journal Title

      J.Clin.Invest. 114

      Pages: 475-484

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible involvement of MIP-1 alpha in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis.2004

    • Author(s)
      Toh K., Kukita T., Wu Z., Kukita A., Sandra F., Tang Q-Y., Nomiyama H., Iijima T.
    • Journal Title

      Lab.Invest. 84

      Pages: 1092-1102

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of the resection of the sciatic nerve on the Th1/Th2 balance in the synovia of the ankle joint of adjuvant arthritic rats.2004

    • Author(s)
      Wu Z., Toh K., Nagata K., Kukita T., Iijima T.
    • Journal Title

      Histochem.Cell Biol. 121

      Pages: 141-147

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Direct stimulation of osteoclastogenesis by MIP-1alpha : evidence obtained from studies using RAW264 cell clone highly responsive to RANKL.2004

    • Author(s)
      Watanabe T., Kukita T., Kukita A., Wada N., Toh K., Nagata K., Nomiyama H., Iijima T.
    • Journal Title

      J.Endocrinol. 180

      Pages: 193-201

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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