Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood

摘要

Osteoclasts (OCs) are specialized bone-resorbing cells. For "in vitro" analysis, they may be obtained from the precursors present in peripheral blood (PB) or umbilical cord blood (UCB), but there has been no detailed analysis of how the kind of source and cell culture conditions may affect the behavior of these cells. Here we analyzed the behavior of OCs after transfection with specific transcription factor decoy molecules founding that the OCs from PB undergo apoptosis when nuclear factor kappa B (NF-kB) or NFATc1 were removed, or when ER alpha expression was increased. Conversely, OCs from UCB showed a strong resistance to apoptotic stimuli. We found that survival signals including Bcl-2, Bcl-XL, and Survivin are present in the OCs/UCB, but not in OCs/PB. The resistance to apoptosis seems to be not correlated with NF-kB, NFATc1, or ER alpha expression level, or with the activation of ERK and Akt proteins. One of the mechanisms responsible for bone remodeling is apoptosis, and being susceptible of therapeutic manipulation, the OCs are extensively employed to investigate cell response to therapies for the treatment of bone loss associated with several diseases, including periodontitis, osteoporosis, and metastatic osteolysis. Therefore, our evidences are to be taken in consideration when both the effects of biological modifiers are tested and OCs apoptosis molecular mechanisms are investigated.