Abstract
BackgroundThe 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.FindingsArticular 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.ConclusionsPGE2 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.
Highlights
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
prostaglandin E2 (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
Summary
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. Connective tissue growth factor/CCN family member 2 (CTGF/CCN2) is a member of the CCN family, which is a group of secreted multifunctional proteins that contain high levels of cysteine (reviewed in [1]). Transforming growth factor (TGF)-b stimulates CTGF expression, and TGF-b-induced CTGF is involved. Despite its potential involvement in OA, the regulatory mechanisms of CTGF expression in chondrocytes have not been fully clarified. Studies using chondrocytic cells and other cell types indicate that CTGF expression is modulated by several factors, including TGF-b [8], dexamethasone[9], and macrophage colony stimulating factor [10].
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