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2002 Fiscal Year Final Research Report Summary

Low Molecular Weight Compounds That Regulate Bone Metabolism

Research Project

Project/Area Number 13460036
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionChubu University

Principal Investigator

NAGAI Kazuo  Chubu University Dept. of Biological Chemistry Professor, 応用生物学部, 教授 (00011974)

Co-Investigator(Kenkyū-buntansha) JE-TAE Woo  Chubu University Dept. of Biological Chemistry Assistant Professor, 応用生物学部, 助教授 (20272693)
Project Period (FY) 2001 – 2002
Keywordsdestruxins / reveromycin A / EGCG / bone resorption / osteoclast / osteoporosis / cell death / calcium
Research Abstract

In the course of screening for the natural compounds in foods and microbial metabolites that prevent or cure osteoporosis, we found destruxins, reveromycin A (RMA) and (-)-Epigallocatechin-3-gallate (EGCG). Cyclodepsipeptides, destruxin B and E, were found to inhibit osteoclastic bone resorption without affecting osteoclast differentiation and survival. Destruxins reversibly induced morphological changes in functional osteoclasts in a dose-dependent manner. Electron microscopical analysis revealed that destruxin-treated osteoclasts on dentine slices have no prominent clear zones or ruffled borders. These results indicate that the anti-resorptive effects result from disorder of morphological structures in polarized osteoclasts induced by destruxins. RMA was found to inhibit bone resorption by inducing apoptosis in mature osteoclasts. The effect of RMA is accompanied by cytochrome c release from mitochondria into cytoplasm, caspase activation and nuclear fragmentation in osteoclasts. RMA … More induced apoptosis in activated osteoclasts having actin ring and resorption capability. The effect of RMA on activated osteoclasts was blocked by concanamycin B, a specific V-ATPase inhibitor or by acetazolamide, a carbonic anhydrase inhibitor, which prevents the acidification around the membrane of osteoclasts. RMA also inhibited the increase of serum calcium concentration induced by PTH injection in TPTX Rat. These results indicate that specific effect of RMA on activated osteoclasts results from acidic condition around the membrane of osteoclasts that increase cell permeability of RMA. Thus, RMA could be a good candidate for a new anti-resorptive osteoporotic medicine with high specificity against activated osteoclasts. EGCG specifically induced cell death in bone resorbing osteoclasts by promoting oxidative stress via Fenton reaction. Specific induction of apoptosis in osteoclasts by EGCG indicated the potentiality of EGCG as a prophylactic or therapeutic agent against osteoporosis. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] J.Ding, K.Nagai, J.T.Woo: "Insulin-dependent adipogenesis in stromal ST2 cells drived from murine bone marrow"Biosci. Biotechnol. Biochem.. 67. 314-321 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakagawa, M.Wachi, J.T.Woo, M.Kato, I.S.Lee, K.Nagai: "Fenton reaction is primarily involved in a mechanism of (-)-epigallocatechin-3-gallate to induce osteoclastic cell death"Biochem. Biophys. Res. Commun.. 292. 94-101 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Igarashi, J.T.Woo, P.H.Stern: "The effects of a selective cyclooxygenase-2 inhibitor, on bone resorption and osteoclastogenesis in vitro"Biochemical Pharmacology. 63. 523-532 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Suda, J.-T.Woo, M.Takami, P M Sexton, K.Nagai: "Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-alpha, IL-1 and RANKL"J. Cell Physiol.. 190. 101-108 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Ding, J.-T Woo, K.Nagai: "The effects of retinoic acid on reversing the adipocyte differentiation into an osteoblastic tendency"Cytotechnology. 36. 125-136 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. Ding, K. Nagai, J.T. Woo: "Insulin-dependent adipogenesis in stromal ST2 cells drived from murine bone marrow"Biosci. Biotechnol. Biochem.. 67. 314-321 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Nakagawa, M. Wachi, J.T. Woo, M. Kato, I.S. Lee, K. Nagai: "Fenton reaction is primarily involved in a mechanism of (-)- epigallocatechin-3-gallate to induce osteoclastic cell death"Biochem. Biophys Res Commun. 292. 94-101 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Igarashi, J.T. Woo and P H Stern: "The effects of a selective cyclooxygenase-2 inhibitor, celecoxib, on bone resorption and osteoclastogenesis in vitro"Biochemical Pharmacology. 63. 523-532 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Suda, J.T. Woo, M. Takami, P M Sexton and K. Nagai: "Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-alpha, IL-1 and RANKL"J. Cell Physiol. 190. 101-108 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Ding, J.T Woo and K. Nagai: "The effects of retinoic acid on reversing the adipocyte differentiation into an osteoblastic tendency"Cytotechnology. 36. 125-136 (2001)

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

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Published: 2004-04-14  

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