title: Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Delta-Prostaglandin J(2).
abstract: 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) 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-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) 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-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) 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.
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ishino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tsubouchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Kohno
authors.forename: Makoto
authors.initials: M
authors.lastname: Wada
authors.forename: Aihiro
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kadoya
authors.forename: Daisaku
authors.initials: D
authors.lastname: Tokunaga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hojo
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Rikio
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa