Destruction of bone and cartilage is the hallmark of autoimmune rheumatoid arthritis (RA). The consequences of this bone loss are painful joint deformities, progressive functional disability. Studies have indicated that osteoclasts are the major cell type in bone resorption in rheumatoid arthritis. Granulocyte-macrophage-CFS (GM-CSF) is a potent proinflammatory cytokine which produced by synovial cells in rheumatoid arthritis to the synovial fluid of the inflamed joint. In this study we provided evidences that bone marrow-derived cells that survive and proliferate in cultures containing high doses of GM-CSF (we have called these GM-BMMs) have high potential to differentiate into osteoclasts in presence of M-CSF and sRANKL. All of the cells in this population were capable to differentiating to TRAP positive osteoclasts and also express high levels of osteoclast markers, CTR and RANK. In view of the large number of macrophages (CD14 positive) found in the RA synovium, osteoclast differentiation by synovial macrophages could represent an important mechanism for the pathogenesis of bone destruction. GM-BMM may represent a macrophage population with high potentiality of osteoclastogenesis in RA site. Therefore GM-BMMs are suitable progenitors to investigate the effect of pro-inflammatory cytokines in osteoclast differentiation and the mechanisms involved bone resorption in diseases like RA. Also in this study we have used a new method for quantification of osteoclast precursors. Unlike previous methods, the present method permits accurate estimates of the number of pre-fusion osteoclast precursors, and also provides a reliable means of quantifying the total number of cells during the culture period (so that the influence of apoptosis and proliferation in cultures can be determined).

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