2003 Fiscal Year Final Research Report Summary
A STUDY ON THE CONTROL OF BONE DESTRUCTION USING OSTEOCLAST DIFFERENTIATION FACTOR AS A TARGET
| Project/Area Number |
13480205
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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 |
Functional biochemistry
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
YASUDA Hisataka THE UNIVERSITY OF TOKYO, INSTITUTE of MEDICAL SCIENCE, LECTURER, 医科学研究所, 講師 (90323641)
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| Co-Investigator(Kenkyū-buntansha) |
SUDO Katsuko THE UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, RESEARCH ASSOCIATE, 医科学研究所, 助手 (50126091)
IWAKURA Yoichiro THE UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, PROFESSOR, 医科学研究所, 教授 (10089120)
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| Project Period (FY) |
2001 – 2003
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| Keywords | BONE DESTRUCTION / OSTEOCLASTS / OSTEOCLAST DIFFERENTIATION FACTOR / OSTEOCLASTOGENESIS INHIBITORY FACTOR / TRANSGENIC MICE |
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| Research Abstract |
Osteoclast differentiation factor, RANKL, is a membrane-bound protein. It is thought that RANKL functions as a membrane-form because osteoclast differentiation requires the interaction between osteoclast progenitors and osteoblasts. Although it is reported that soluble RANKL (sRANKL) is produced by activated T -cells and sRANKL is involved in the inflammatory bone destruction, the function of sRANKL is unknown. We generated transgenic (TG) mice overexpressing sRANKL to investigate the physiological roles of sRANKL. The TG mice as well as osteoclastogenesis inhibitory factor, osteoprotegerin (OPG)-deficient (KO) mice exhibited severe osteoporosis. These results suggest that overexpresssion of sRANKL in vivo due to pathological conditions such as inflammation results in bone destruction. The number of osteoclasts increases in both sRANKL-TG nice and OPG-KO mice by the similar mechanism that the increase of the ratio of RANKL and OPG in bone causes osteoclast differentiation. The coupling between bone formation and bone resorption observed in OPG-KO mice was not observed in sRANKL-TG mice. The detailed comparison of the phenotypes of the two types of mice will facilitate the identification of the coupling mechanism and coupling factors involved in the process.
Runx2 is the transcription factor essential for osteoblast differentiation. Runx2-KO mice have cartridge but lack osteoblasts and bone. Runx2-KO mice almost lack osteoclasts probably due to the absence of osteoblasts. We mated Runx2-KO mice and sRANKL-TG mice to investigate the mechanism by which Runx2-KO mice lack osteoclasts. The number of osteoclasts increased in Runx2-KO/sRANKL-TG mice, suggesting that the osteoclast differentiation in Runx2-KO/sRANKL-TG mice was restored by sRANKL and that osteoblasts differentiated by Runx2 was the source of RANKL.
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