| Project/Area Number |
12307031
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | The University of Tokyo |
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Principal Investigator |
NAKAMURA Kozo Faculty of Medicine, Professor, 医学部附属病院, 教授 (60126133)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sakae Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50282661)
SEICHI Atsushi Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70236066)
KAWAGUCHI Hiroshi Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (40282660)
NAGAI Ryozo Faculty of Medicine, Professor, 医学部附属病院, 教授 (60207975)
OYANAGI Kiyomi Tokyo Metropolitan Institute for Neuroscience, Chief Researcher, 副参事研究員 (00134958)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥34,850,000 (Direct Cost: ¥29,600,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2002: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2001: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2000: ¥12,100,000 (Direct Cost: ¥12,100,000)
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| Keywords | Klotho / gene analysis / ageing / bone / spine / nerve / muscle / 網膜 / klotho / 遺伝子導入 |
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| Research Abstract |
The mouse homozygous for a disruption of the klotho locus (klotho mouse) exhibited multiple pathological conditions resembling human ageing. We observed osteopenia in klothomce with a low bone turnover, in which the decrease in bone formation exceeded the decrease in bone resorption and resulted in the net bone loss. The number of B lymphocytes was decreased in the klotho bone marrow, suggesting the role of the cells in osteoclastogenesis. Morphological observation of the spinal cord revealed the decrease in Nissle bodies and abnormality of the rER. We then explored whether human klotho gene polymorphism is associated with age-related skeletal disorders : osteoporosis and spondylosis. The microsatellite polymorphism of the klotho gene was shown to be a candidate for the genetic regulation of osteoporosis and spondylosis. We further examined the association between klotho gene polymorphisms and bone density in two genetically distinct racial populations: the Caucasian and the Japanese. Screening of single-nucleotide polymorphisms (SNPs) in the human klotho gene identified a total of 11 polymorphisms, and three of them were common in both populations. One in the promoter region was strongly associated with bone density in aged postmenopausal women (【greater than or equal】65 yrs.), but not in premenopausal or younger postmenopausal women. An electrophoretic mobility shift analysis revealed that the G->A substitution in the promoter region affected DNA-protein interaction. These results indicate that the klothogem may be involved in the pathophysiology an age-related disorder in humans.
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