1997 Fiscal Year Final Research Report Summary
Regulation of PGE synthesis by activated cytosolic phospholipase A2 and induced cyclooxygenase-2 in osteoblasts.
| Project/Area Number |
08457493
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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 basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
MIYAURA Chisato Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (20138382)
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| Co-Investigator(Kenkyū-buntansha) |
JIMI Eijiro Showa University, School of Dentistry, Assistant, 歯学部, 助手 (40276598)
UDAGAWA Nobuyuki Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
SUDA Tatsuo Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)
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| Project Period (FY) |
1996 – 1997
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| Keywords | prostaglandin / interleukin-1 / osteoblast / phospholipase A2 / cyclooxygenase / platelet-derived growth factor |
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| Research Abstract |
The synthesis of prostaglandins (PGs) is regulated by the arachidonic acid release by phospholipase A2 (PLA2) and its conversion to PGs by cyclooxygenase (COX). In the present study, we examined the regulation of PG synthesis by interleukin (IL) -1 in mouse osteoblasts. Although IL-1 greatly enhanced COX-2 mRNA expression and its protein levels, PGE2 was not produced until 24 h.When arachidonic acid was added to osteoblasts precultured with IL-1, PGE2 was produced within 10 min.Of several growth factors tested, platelet-derived growth factor (PDGF) specifically initiated the synthesis of PGE2, which was markedly suppressed by a selective inhibitor of COX-2 (NS-398). In mouse osteoblasts, cytosolic PLA2 (cPLA2) mRNA and its protein were constitutively expressed and moderately increased by IL-1. PDGF markedly stimulated PLA2 activity, which was blocked by a cPLA2 inhibitor. The PDGF-induced activation of cPLA2 was accompanied by phosphorylation of its protein. On the other hand, IL-1 and IL-6 cooperatively induced COX-2 gene expression and stimulated PGE2 synthesis in co-culture of bone marrow cells and osteoblasts and in organ culture of new born mouse calvaria. In these culture system, FCS or endogenous bone marrow-derived growth factor were enough to activate cPLA2. These results indicated that cPLA2 activation by growth factor such as PDGF is essential for IL-1-induced and COX-2-dependent PGE synthesis in mouse osteoblasts.
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