| Project/Area Number |
10671371
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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 | Sapporo Medical University |
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Principal Investigator |
WADA Takuro Sapporo Medical University School of medicine, Associate Professor, 医学部, 助教授 (00244369)
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| Co-Investigator(Kenkyū-buntansha) |
KOKAI Yasuo Sapporo Medical University School of medicine, Associate Professor, 医学部, 助教授 (20178239)
ISHII Seiichi Sapporo Medical University School of medicine, Professor, 医学部, 教授 (20001000)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | G-CSF / osteoporosis / transgenic mice / osteoclasts / osteoblasts / BMP-2 / Toll-like receptor / lung adenocarcinoma / 骨量 / 骨形成 / Bone morphogenic protein |
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| Research Abstract |
(1) We have shown that ectopic bone formation induced by BMP-2 was impaired in transgenic mice overproducing G-CSF. In G-CSF mice, induction of mesenchymal cells and chondrogenesis diminished at early stage of ectopic bone formation. The lamellar structure was immature and the calcium content was decreased in the ectopic bone of G-CSF mice 3 weeks after the implantation of BMP-2. There was no significant difference in mRNA expression levels of type I-collagen, osteopontin, and osteocalcin in the ectopic bone among G-CSF mice and their littermate controls. However, the expression of osteocalcin protein in the ectopic bone matrix was less in G-CSF mice than that in littermates.
(2) The effect of vitamin K2 (menatetrenone) (MK4) on bone phenotypes during development was examined. Mice were fed chow k containing either 0.05mg MK-4/100g or 20.0mg MK-4/100g for twelve weeks as the control and experimental diets, respectively.This treatment did not change bone length, irrespective of the type of mice or diet. Peripheral quantitative computed tomography(pQCT)revealed an increase of the CT value in bone in MK-4 treated mice.
(3) We investigated the cellular and molecular abnormality in the bone of G-CSF mice using ex-vivo cell culture system. Here we demonstrate that osteoblast progenitors in bone marrow oftransgenic mice are diminished in number but possess increased ability to support osteoclastgenesis. CFU-GM in bone marrow cells, which is blieved to contain osteoclast progenitors, was significantly increased in transgenic mice. In addition, the expression of receptor activator of nuclear factor- κ B ligand (RANK ligand ; RANKL) was rather decreased in osteoblasts oftransgenic mice.
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