title: Prostaglandin E2 regulates the expression of connective tissue growth factor (CTGF/CCN2) in human osteoarthritic chondrocytes via the EP4 receptor.
abstract: BACKGROUND
  The regulatory mechanisms of the expression of connective tissue growth factor/CCN family member 2 (CTGF/CCN2) in human articular chondrocytes have not been clarified. We investigated the effect of prostaglandin E2 (PGE2) on CTGF/CCN2 expression in chondrocytes.
  
  
  RESULTS
  Articular cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were isolated and cultured in vitro. Chondrocytes were stimulated with PGE2, PGE receptor (EP)-specific agonists, or interleukin (IL)-1. CTGF expression was analyzed using quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. The inhibitory effects of EP receptor antagonists (for EP2 and EP4) against PGE2 stimulation were also investigated. Stimulation of chondrocytes with PGE2 or IL-1 significantly suppressed CTGF expression. The suppressive effect of PGE2 was reproduced by EP2/EP4 receptor agonists but not by EP1/EP3 receptor agonists, and was partially blocked by an EP4 receptor antagonist, suggesting that the EP4 receptor has a dominant role.
  
  
  CONCLUSIONS
  PGE2 may be involved in the regulation of CTGF/CCN2 expression in human articular chondrocytes via the EP4 receptor. Elucidation of EP4-mediated signaling in chondrocytes may contribute to a better understanding of the effects of PGE2 in arthritis.
authors.affiliation: Department of Biochemistry, St, Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Masuko
authors.forename: Minako
authors.initials: M
authors.lastname: Murata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yudoh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato