Introductions: There are increasing evidences for distinct monocyte subpopulations within human peripheral blood. Human monocytes are commonly considered to be non-proliferating; however, we and others have defined a subpopulation of human monocytes which is capable of proliferating in vitro, in response to CSFs (for example macrophage colony-stimulating factor (M-CSF). Because of their proliferative capacity it is reasonably assumed that these cells are less mature than the bulk of the non-proliferating monocytes. It has been suggested that this proliferative monocytes (PM) still has some criteria of oligopotent stem cells with potential to differentiate to mature monocyte further in the peripheral blood or monocyte /macrophage lineage cells such as osteoclast later in tissues. Osteoclasts are cells that responsible for bone resorption. During clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The hypothesis governing in this study is that this PM subpopulation is the small pool of circulating osteoclast precursors in human peripheral blood monocytes. Methods Human peripheral blood monocytes of 13 donors were labelled with CFSE and then cultured in presence of M-CSF for 9 day. CFSE-labelled cells were then sorted into proliferating or nonproliferating cells. The sorted cells were cultured in presence of M-CSF and receptor activator of nuclear factor-kappa-B ligand (RANKL) to differentiate into osteoclasts. Results: Our results indicated that the PM monocytes gave rise to significantly more TRAP multinucleated cells, with higher osteoclast gene expression and significantly more bone resorbing capability than the bulk of the monocytes. Conclusion: PM monocyte population has higher differentiation plasticity than a nonproliferative population and is highly capable of differentiating into osteoclasts, at least after culture. These results supported our hypothesis that the PM subpopulation of CD14+ peripheral blood monocytes is a less mature population, with capability to differentiate to other cell types. This proliferative human monocyte subpopulation has the potential to be used in vitro for generating large numbers of human osteoclasts. This system can be used to explore the

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