Synergistic induction of matrix metalloproteinase 1 by interleukin-1? and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism

Abstract

Since no changes in receptor expression were observed, receptor modulation cannot account for the IL-1alpha/OSM synergy observed. Instead, the interplay of various intracellular signaling pathways is a more likely explanation. STAT activation is required, but STAT proteins do not interact directly with the MMP-1 promoter. We propose that activated STATs stimulate c-fos expression, and changes in expression of the AP-1 components regulate MMP-1 expression. We highlight a new mechanism for MMP-1 regulation in human chondrocytes that could provide potential new therapeutic targets.