['To investigate the role of T cell induction of matrix metalloproteinase 13 (MMP-13) production by human osteoblasts in order to better understand the process of bone loss in rheumatoid arthritis (RA).', 'Activated T cell-conditioned medium (ACTTCM) was used to mimic the physiologic conditions of inflammation. MMP-13 production by human osteoblasts was assessed using a specific enzyme-linked immunosorbent assay. Specific inhibitors of the p38 mitogen-activated protein (MAP) kinase and the extracellular signal-regulated kinase 1/2 (ERK-1/2) MAP kinase signaling pathways were used to assess their roles in T cell-mediated MMP-13 production. Finally, recombinant cytokines representative of the major components in ACTTCM were assessed for their ability to induce MMP-13.', 'ACTTCM powerfully induced MMP-13 in human osteoblasts. Inhibition of p38 activity abolished, while inhibition of ERK-1/2 activity enhanced, MMP-13 production. We next investigated physiologic levels of the T cell cytokines tumor necrosis factor alpha (TNFalpha), transforming growth factor beta (TGFbeta), interferon-gamma (IFNgamma), and interleukin-17 (IL-17) for their roles in MMP-13 induction. Although individual cytokines had no significant effect, the combination of TNFalpha, TGFbeta, IFNgamma, and IL-17 resulted in a dramatic p38-dependent induction of MMP-13 identical to that produced by ACTTCM.'] Do t cells regulate the expression of matrix metalloproteinase in human osteoblasts via a dual mitogen-activated protein kinase mechanism?