Introduction: bone loss is one of the major pathological effects in rheumatoid arthritis (RA). Studies have indicated that osteoclasts are the major cell type in bone resorption in RA. Granulocyte-macrophage-CSF (GM-CSF) is a potent proinflammatory cytokine. Although is difficult to detect GM-CSF normally in the circulation it is induced in the synovial fluid of the inflamed joint. Method: Bone marrow cells were cultured in high dosage of GM-CSF and/or M-CSF for 7 days. The GM-CSF bone marrow derive cells (GM-BMM) or M-CSF derive macrophages (M-BMM) were cultured with soluble RANKL and M-CSF. Results: We provided evidences that GM-BMM have high osteoclastogenesis potential. All of the cells in this population were capable to differentiating to TRAP positive osteoclasts and also in compare with M-BMM, GM-BMM generate more multi nucleuses osteoclast (p>0.01) and express higher levels of osteoclast markers CTR, Cath k, c-fos and β3- integrin as measured by Q-PCR (at least more than 2 fold). Furthermore when bone marrow cultured in both M-CSF and GM-CSF, GM-CSF had dominate effects on potentiality of cell to differentiate. Conclusions: We found that GM-BMM precursors represent an easily obtainable and enrich source of osteoclast progenitors, with a strong osteoclastogenic potential. GM-BMM 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 view of the large infiltration of macrophages in the RA synovium, our data suggesting synovial macrophages might have a higher potentiality to differentiate to osteoclast.

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