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2004 Fiscal Year Final Research Report Summary

Study of the molecular mechanism of osteoclast apoptosis.

Research Project

Project/Area Number 15390450
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YAMAMOTO Aiichiro  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (90359612)

Co-Investigator(Kenkyū-buntansha) TANAKA Sakae  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (50282661)
ODA Hiromi  Saitama medical University, School of Medicine, Professor, 医学部, 教授 (60101698)
Project Period (FY) 2003 – 2004
KeywordsOsteoclast / Apoptosis / Bim
Research Abstract

Osteoclasts are multinucleated giant cells primarily responsible for bone resorption. They are terminally differentiated cells, and undergo rapid apoptosis in the absence of trophic factors such as macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Osteoclasts undergo rapid apoptosis without trophic factors, such as macrophage colony-stimulating factor (M-CSF). Their apoptosis was associated with a rapid and sustained increase in the pro-apoptotic BH-3-only Bcl-2 family member Bim. This was caused by the reduced ubiquitination and proteasomal degradation of Bim that is mediated by c-Cbl. Although the number of OCs was increased in the skeletal tissues of bim-/-mice, the mice exhibited mild osteosclerosis due to reduced bone resorption. OCs differentiated from bone marrow cells of bim-/-animals showed a marked prolongation of survival in the absence of M-CSF, compared to bim+/+ OCs, but the bone-resorbing activity of bim-/-OCs was significantly reduced. Overexpression of a degradation-resistant lysine-free Bim mutant in bim-/-cells abrogated the anti-apoptotic effect of M-CSF, while wild type Bim did not. These results demonstrate that ubiquitination-dependent regulation of Bim levels is critical for controlling apoptosis and activation of OCs.

  • Research Products

    (3 results)

All 2003

All Journal Article (3 results)

  • [Journal Article] Signal transduction pathways regulating osteoclast differentiation and function.2003

    • Author(s)
      Tanaka, S., Nakamura, I., Inoue, J., Oda, H., Nakamura, K.
    • Journal Title

      J Bone Miner Metab 21

      Pages: 123-133

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppression of arthritic bone destruction by adenovirus-mediated dominant negative ras gene transfer to synoviocytes and osteoclasts.2003

    • Author(s)
      Yamamoto A, Fukuda A, Seto H, Miyazaki T, Kadono Y, Sawada Y, Nakamura I, Katagiri H, Asano T, Tanaka Y, Oda H, Nakamura K, Tanaka S.
    • Journal Title

      Arthritis Rheum 48

      Pages: 2682-2692

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of Osteoclast Apoptosis by Ubiquitination of Proapoptotic BH3-only Bcl-2 Family Member Bim.2003

    • Author(s)
      Akiyama T, Bouillet P, Miyazaki T, Kadono Y, Chikuda H, Chung U, Fukuda A, Hikita A, Seto H, Okada T, Inaba T, Sanjay A, Baron R, Kawaguchi H, Oda H, Nakamura K, Strasser A, Tanaka S.
    • Journal Title

      Embo J 22

      Pages: 6653-6664

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

URL: 

Published: 2006-07-11  

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