2003 Fiscal Year Final Research Report Summary
Functional analysis of TNF signaling in bone metabolism using knocked-out mice of type I and II TNF receptors.
| Project/Area Number |
14571385
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagasaki University |
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Principal Investigator |
ENOMOTO Hiroshi Nagasaki University, Graduate School of Biomedical Science, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (90284679)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Akira Nagasaki University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (00142430)
OKANO Kunihiko Nagasaki University, Hospital of Medicine & Dentistry, Assistant Professor, 医学部・歯学部附属病院, 助手 (70325645)
SHINDO Hiroyuki Nagasaki University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (30107677)
ITO Masako Nagasaki University, Hospital of Medicine & Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (10193517)
TSUKAZAKI Tomoo Nagasaki University, Graduate School of Biomedical Science, Assistant Professor, 大学院・医歯薬学総合研究科, 助教授 (50315230)
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| Project Period (FY) |
2002 – 2003
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| Keywords | TNF receptor / knock-out mice / osteoclasts / 破骨細胞 |
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| Research Abstract |
TNF signaling is known to play a crucial role in bone absorption under inflammatory condition. To distinguish the functional role of type I and type II TNF receptor, knock-out mice of each receptor were subjected to histological and bone morphometric analysis. In 12 wks old femurs, bone volume, thickness and mineral content in both cortical and cancellous bone were decreased in type I (-/-) mice, whereas these parameters were increased in type II (-/) mice. To investigate a molecular mechanism of TNF receptor involved bone metabolism, osteoblasts and osteoclasts were cultured from calvariae and macrophage from bone marrow, respectively. Treatment of osteoblasts with BMP-2 or Dexamethasone, however, did not alter their ALP expression as well as cell proliferation. In contrast, osteoclast formation was only induced in type II (-/-) macrophage by treating with M-CSF and RANKL, indicating that certain molecules secreted of exposed on cell surface could be important for osteoclasts formation. To identify these molecules, we applied DNA tip analysis to each cultured cell and found three novel and 5 known genes that could be target or down-stream signaling for TNF receptor activation. We are now analyzing the functional role and expression pattern of these genes.
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Research Products
(8 results)
