analysis of the mechanism of bone and joint destruction by beta2-microglobulin amyloid deposion
| Project/Area Number |
26860236
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | University of Fukui |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
NAIKI Hironobu 福井大学, 医学部, 教授 (10227704)
HASEGAWA Kazuhiro 福井大学, 医学部, 助教 (60324159)
OZAWA Daisaku 福井大学, テニュアトラック推進本部, 助教 (60554524)
|
|---|
| Project Period (FY) |
2014-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | アミロイドーシス / β2-ミクログロブリン / 細胞毒性 / 滑膜細胞 / エンドサイトーシス / リソソーム / 滑膜線維芽細胞 / 血液透析 / 透析アミロイドーシス |
|---|
| Outline of Final Research Achievements |
In dialysis-related amyloidosis, β2-microglobulin (β2-m) amyloid fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome and destructive arthropathy, but the mechanism by which these amyloid fibrils destruct bone and joint tissue is not fully understood. In this study, we assessed the cytotoxic effect ofβ2-m amyloid fibrils on the cultured rabbit synovial fibroblasts. β2-m amyloid fibrils exerted the toxic effect on the synovial fibroblasts. When the cells were incubated with amyloid fibrils, many endosomes/lysosomes filled with amyloid fibrils were observed. Moreover, some endosomal/lysosomal membranes were disrupted by intravesicular fibrils, leading to the leakage of the fibrils into the cytosol and adjacent to mitochondria. Inhibition of endocytosis by cytochalasin D attenuated the toxicity of amyloid fibrils. These results suggest that endocytosed β2-m amyloid fibrils induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes.
|
Report
(3 results)
Research Products
(5 results)
