title: Regulation of Collagen Gene Expression by Prostaglandins and Interleukin-1beta in Cultured Chondrocytes and Fibroblasts.
abstract: To compare the modulatory effects of different prostaglandins on collagen gene expression in human chondrocytes, PGE(2), PGE(1), misoprostol (PGE(1) analog), and PGF(2alpha) (10, 50 and 100 ng ml(minus sign1)) were added to human chondrocytes with or without interleukin-1beta (IL-1beta) in the presence of indomethacin to inhibit endogenous prostaglandin synthesis and the effects evaluated on chondrocyte morphology, collagen synthesis, and procollagen mRNA levels. The effects of prostaglandins on the expression of collagen gene regulatory sequences were examined using transient transfection assays of reporter gene constructs in human chondrocytes and BALB/c3T3 fibroblasts, PGE(1), misoprostol, and PGF(2alpha), similar to PGE(2), inhibited type I collagen gene expression in fibroblasts and promoted type II collagen gene expression in chondrocytes. PGE(2), the major inflammatory prostaglandin produced by IL-1-activated chondrocytes and fibroblasts, and PGF(2alpha) were somewhat more potent than the anti-inflammatory prostaglandins PGE(1) and misoprostol in counteracting the IL-1-induced suppression of type II collagen gene expression by chondrocytes and stimulation of type I collagen gene expression by fibroblasts. Rather than promoting degradation of the cartilage matrix in joint diseases, prostaglandins may be somewhat protective, suppressing fibrosis, and maintaining or promoting appropriate cartilage repair.
authors.affiliation: Massachusetts General Hospital, Charlestown, and Harvard Medical School, Boston, USA.
authors.forename: Mary B.
authors.initials: MB
authors.lastname: Goldring
authors.forename: Lii-Fang
authors.initials: LF
authors.lastname: Suen
authors.forename: Rina
authors.initials: R
authors.lastname: Yamin
authors.forename: Wen-Fu Thomas
authors.initials: WF
authors.lastname: Lai