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2004 Fiscal Year Final Research Report Summary

A study of cross-talk between the expression mechanisms of osteoclast differentiation factor (ODF) and osteoclastogenesis inhibitory factor (OCIF)

Research Project

Project/Area Number 15390465
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionSaitama Medical School

Principal Investigator

SUDA Tatsuo  Saitama Medical School, School of Medicine, Professor, 医学部, 教授 (90014034)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Takenobu  Saitama Medical School, School of Medicine, Associate Professor, 医学部, 助教授 (80245802)
TAKAMI Masamichi  Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (80307058)
Project Period (FY) 2003 – 2004
Keywordsosteoblasts / osteoclasts / ODF / OCIF / microarray / transcriptional control / bone resorption / calcium regulatory hormones
Research Abstract

Bone is a dynamic tissue that is formed and remodeled by continuously occurring bone formation and resorption. Osteoblasts are involved not only in bone formation, but also in bone resorption via inducing osteoclast differentiation factor (ODF)/receptor activator of NF-kB ligand (RANKL) and its antagonist, osteoclastogenesis inhibitory factor OCIF)/osteoprotegerin (OPG) in osteoblasts. In the present study, we examined a potential regulatory mechanism of RANKL and OPG expression by bone-resorbing hormones in osteoblasts. Both 1,25(OH)_2D_3 and parathyroid hormone (PTH) induced RANKL mRNA expression and inhibited OPG mRNA expression. These effects of PTH reached a peak within 3 h, then sharply decreased thereafter, whereas those of 1,25(OH)_2D_3 gradually increased up to 10 h and were kept until 24 h. The effects of 1,25(OH)_2D_3 were blocked by adding cychloheximide but not MAP kinase inhibitors, suggesting that dc novo protein synthesis is essential for the l,25(OH)_2D_3 effects. Target genes of 1,25(OH)_2D_3 were analyzed by microarray analysis. Vitamin D receptor (VDR), interleukin 4 receptor a (IL4Ra) and a RNA helicase (Ddx21), were up-regulated more than 2 fold, and serum/glucocorticoid- regulated kinase (Sgk) was down-regulated more than 0.5 fold in osteoblastic cells by 1,25(OH)_2D_3. Transient over-expression of VDR, IL4Ra or Ddx21 in osteoblasts decreased the levels of RANKL mRNA induced by 1,25(OH)_2D_3. VDR increased the basal level of RANKL mRNA. However, none of them affected OPG mRNA levels irrespective of the presence and absence of 1,25(OH)_2D_3. Taken together, these results suggest that VDR, IL4Ra and Ddx21 are involved in the RANKL expression induced by 1,25(OH)_2D_3. Different transcription factors may regulate mRNA expression of RANKL and OPG in response to 1,25(OH)_2D_3.

  • Research Products

    (10 results)

All 2005 2004

All Journal Article (10 results)

  • [Journal Article] Vitamin D and osteoclastogenesis2005

    • Author(s)
      Yasuda H, Higashio K, Suda T
    • Journal Title

      Vitamin D, Elsevier 2^<nd> Edition

      Pages: 665-685

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Feldman, Vitamin D and osteoclastogenesis2005

    • Author(s)
      Hisataka Yasuda, Kanji Higashio, Tatsuo Suda
    • Journal Title

      In Vitamin D, 2^<nd> edition (ed. D. W. Pike, and F. Glorieux) (Elsevier)

      Pages: 665-685

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] ビタミンDと骨2004

    • Author(s)
      須田 立雄
    • Journal Title

      Osteoporosis Japan 12(2)

      Pages: 356-357

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 硬組織の起源と進化 序説2004

    • Author(s)
      須田 立雄
    • Journal Title

      The Bone 18(4)

      Pages: 421-426

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 骨粗鬆症の成因研究の現状2004

    • Author(s)
      須田 立雄, 宮浦 千里
    • Journal Title

      日本臨床 62(2)

      Pages: 13-20

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Vitamin D and bone -How does vitamin D regulate bone formation and resorption?-2004

    • Author(s)
      Suda T
    • Journal Title

      Proceedings of the Japan Academy, Ser.B 80(9)

      Pages: 407-421

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Vitamin D and bone2004

    • Author(s)
      Tatsuo Suda
    • Journal Title

      Osteoporosis Japan 12

      Pages: 356-357

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The origin and evolution of bone tissue -prologue-2004

    • Author(s)
      Tatsuo Suda
    • Journal Title

      The Bone 18

      Pages: 421-426

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recent advance in basic research for osteoporosis2004

    • Author(s)
      Tatsuo Suda, Chisato Miyaura
    • Journal Title

      Nippon Rinsho 62 (supplement 2)

      Pages: 13-20

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vitamin D and bone -How does vitamin D regulate bone formation and resorption?-2004

    • Author(s)
      Tatsuo Suda
    • Journal Title

      Proceedings of The Japan Academy, Ser. B 80

      Pages: 407-421

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

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Published: 2006-07-11  

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