2004 Fiscal Year Final Research Report Summary
Study of the molecular mechanism of osteoclast apoptosis.
| Project/Area Number |
15390450
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | The 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
|
| Keywords | Osteoclast / 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)
-
-
[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
