The release of MPs was induced in apoptotic as well as stimulated cells. Morphological analysis of MPs by electron microscopy showed a population of circular membrane blebs ranging from 200 to 700 μm. MPs from all cell types induced strongly the synthesis of mRNA for MMP-1 (72 ± 13-fold), MMP-3 (80 ± 10-fold), MMP-9 (18 ± 4-fold) and MMP-13 (37 ± 2-fold) in RASF in a dose-dependent manner. Similar effects were seen on osteoarthritis synovial fibroblasts and normal synovial fibroblasts. The induction of matrix metalloproteinases (MMPs) was time dependent, with effects primarily seen after 36 hours. The dose-dependent upregulation of biologically active MMPs was also observed on the protein level. The induction was specific for the aforementioned MMPs with no induction seen for MMP-2, MMP-14 or TIMP-1, TIMP-2 and TIMP-3. MPs also increased the synthesis of mRNA for IL-6 (27 ± 6-fold), IL-8 (35 ± 3-fold), MCP-1 (5 ± 1-fold) and MCP-2 (27 ± 3-fold) in synovial fibroblasts. No differences in cell viability were observed between fibroblasts stimulated by MPs and controls. In Iκ-B-transfected RASF, MMPs were 50–75% less inducible by MPs compared with wild-type synovial fibroblasts. The stimulation of NF-κB-dependent pathways by MPs was confirmed by EMSA.