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标题：Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2
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作者：Hidetaka Ishino ; Yutaka Kawahito ; Yasunori Tsubouchi 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2008
卷号：42
期号：1
页码：64-69
DOI：10.3164/jcbn.2008011
出版社：The Society for Free Radical Research Japan
摘要：15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ₂ can suppress interleukin (IL)-1β-induced prostaglandin E₂ (PGE₂) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE₂ synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ₂ led to a significant increase in IL-1α-induced COX-2 expression and PGE₂ production in a dose dependent manner. The effect of 15d-PGJ₂ was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ₂ exerts a positive feedback regulation of the arachidonate cascade of PGE₂ in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.
关键词：15d-PGJ2;PPAR-γ;osteoblast;PGE2;COX-2