Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. Since matrix metalloproteinases (MMPs) are involved in joint and bone damage in inflammatory and infectious diseases, we investigated the production of MMPs by human osteoblasts and monocytes, either upon Brucella abortus infection or upon reciprocal stimulation with factors produced by each infected cell type. B. abortus infection of the normal human osteoblastic cell line hFOB 1.19 triggered a significant release of MMP-2, which was mediated in part by granulocyte-macrophage colony-stimulating factor (GM-CSF) acting on these same cells. Supernatants from infected osteoblasts exhibited increased levels of monocyte chemoattractant protein 1 and induced the migration of human monocytes (THP-1 cell line). Infection with B. abortus induced a high MMP-9 secretion in monocytes, which was also induced by heat-killed B. abortus and by the Omp19 lipoprotein from B. abortus. These effects were mediated by Toll-like receptor 2 and by the action of tumor necrosis factor alpha (TNF-␣) produced by these same cells. Supernatants from B. abortus-infected monocytes induced MMP-2 secretion in uninfected osteoblasts, and this effect was mediated by TNF-␣. Similarly, supernatants from infected osteoblasts induced MMP-9 secretion in uninfected monocytes. This effect was mediated by GM-CSF, which induced TNF-␣ production by monocytes, which in turn induced MMP-9 in these cells. These results suggest that MMPs could be potentially involved in the tissue damage observed in osteoarticular brucellosis.Brucellosis is a multisystemic debilitating disease caused by Brucella spp., which may eventually become chronic. Humans usually get the infection from contact with infected animals and animal products, particularly milk and cheese (45). Brucellosis manifestations are mainly due to inflammatory phenomena, which may be found both in the acute and chronic phases of the disease and in virtually all of the affected organs (39).Osteoarticular involvement, including spondylitis, sacroiliitis, osteomyelitis, peripheral arthritis, bursitis, and tenosynovitis, represents the most common complication of brucellosis affecting up to 85% of patients (3,17,24,29,41,48).While the clinical and imaging aspects of osteoarticular brucellosis have been described widely, the cellular and molecular pathogenic mechanisms of joint and bone disease caused by Brucella have been virtually ignored. A septic form of brucellar arthritis is supported by the isolation of Brucella spp. from synovial fluid or tissue from affected patients (20,35). In addition, previous studies performed in our laboratory showed that Brucella spp. can infect and survive within human osteoblastic cell lines (11).In different conditions, not only cytokines and chemokines but also matrix metalloproteinases (MMPs) are usually released within the inflammatory milieu. MMPs comprise a large family of Zn 2ϩ -and Ca 2ϩ -dependent endopeptidases whose capacity to degrade extracell...