| Project/Area Number |
16390446
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
NAKAMURA Toshitaka University of Occupational and Environmental Health, Japan, School of Medicine, Professor (50082235)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Akinori University of Occupational&Environmental Health, Japan, School of Medicine, Associate Professor (90248576)
OKIMOTO Nobukazu University of Occupational&Environmental Health, Japan, School of Medicine, Part-time Doctor (70330991)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,130,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥630,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | loading / bone / LDL / osteoblast / bone marrow cell / LRP5 / Wnt / PTH / 脂肪細胞 / 脂質 / LDL / 酸化LDL / 骨形成 / アポトーシス / p53 / オステオカルシン / アポリポプロテインE / 高脂質食 / 過酸化脂質 / 非荷重 / 不動 / 海綿骨 / 破骨細胞 / RANKL / Mac-1 |
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| Research Abstract |
The results during the 4-year research period were summarized as follows.
1) The trabecular bone volume, bone formation rate, and osteoblast surface were reduced in the mice fed with high-fat diet compared with the mice fed with standard diet. The serum levels of low-density lipoprotein (LDL) and oxidized LDL were elevated in the mice fed with high-fat diet compared with the mice fed with standard diet. LDL and oxidized LDL induced apoptosis of osteoblasts in the cell culture study.
2) Fat tissue stained by oil-red O was reduced and bone tissue was increased in the histological sections 7 days after climbing exercise. In the bone marrow cells of climbing mice (intermittent skeletal loading model mice), LRP5 (LDL receptor-related protein 5) and wnt/β-catenin mRNA expressions were enhanced through PTH/PTHrP receptor signal 4 days after climbing exercise. C/EBPβ and C/EBP8 decreased 4 days, and aP2 and PEPCK decreased 7 days after climbing exercise. We resulted that climbing exercise inhibits adipogenic differentiation and promotes osteogenic differentiation by highly expressed LRP-5 and wnt/β-catenin mRNA through PTH/PTHrP receptor.
3) We clarified the association of radiological findings of spinal osteoarthritis with genetic type of Wnt-1-induced secreted protein 1 (WISP1) or with single-nucleotide polymorphism of LRP5 in postmenopausal Japanese women.
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