IL-1 beta-induced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27)

The purpose of this study was to examine how chondrocytes are involved in t he molecular mechanism of inflammation in rheumatoid arthritis (RA). A chon drosarcoma cell line (OUMS-27) was cultured and treated with interleukin-1 beta (IL-1 beta). Changes in the expression levels of matrix metalloprotein ase-1 (MMP-1), metalloproteinase-13 (MMP-13), and gliostatin/platelet-deriv ed endothelial cell growth factor (GLS/PD-ECGF) were assessed by reverse tr anscription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorb ent assays. IL-1 beta induced the expressions of MMP-1, MMP-13, and GLS mRN As and proteins in a dose-dependent manner. Selective inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway with SB 203580 and SB 202190 blocked the expression of MMP-1, MMP-13, and GLS more strongly than selective inhibition of the extracellular signal-regulated kinase 1 and 2 ( ERK1/2) pathway by PD 98059. These findings suggest that chondrocytes may i ntensify cartilage destruction and inflammation in RA by the induction of M MP-1, MMP-13, and GLS by IL-1 beta and that the p38 MAPK pathway plays an i mportant role in these inductions.