| Project/Area Number |
13680682
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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 |
Structural biochemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SAKAMOTO Kazuichi Univ. Tsukuba, Inst. Biological Sciences, Associate Professor, 生物科学系, 助教授 (90235169)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hideyo Univ. Tsukuba, Inst. Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (60235380)
BANNAI Shiro Univ. Tsukuba, Inst. Basic Medical Sciences, Professor, 基礎医学系, 教授 (70019579)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Prostaglanidn / Receptor / Osteoclast / Oxydative Stress / Regulatory Protein |
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| Research Abstract |
Prostaglandin (PG) E2 is a known bone absorbing agent that act on osteoblasts to facilitate osteoclastogenesis by increasing the secretion of RANKL. In the present study, we investigated the direct action of PGE2 on osteoclastic progenitors that differentiate into TRAP-positive multinucleated cells. The hematopoietic stem cell obtained from murine bone : marrow was purified by a Sephadex-GlO column, and cultured in the presence of CSF-1 and RANKL to facilitate cell differentiation. The introduction of low-density PGE2 into the culture resulted in a drastic increase of TRAP-positive multinucleated cells, whereas the addition of high-density PGE2 had the opposite effect. PCR analysis revealed increased level of EP3 mRNA in undifferentiated cells and reduced level after the development of osteoclast ; EP1, EP2 and EP4 were constitutively expressed throughout the differentiation. Investigation of intracellular signaling verified that low-density PGE2 suppressed PKA activity in undifferentiated cells, suggesting that PGE2 acts on the osteoclastic cell lineage to facilitate cell differentiation by suppressing PKA in the presence of RANKL.
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