Human osteoclasts differentiated from umbilical cord blood precursors are less prone to apoptotic stimuli than osteoclasts from peripheral blood.
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 ERalpha 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 ERalpha 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.
Penolazzi
Letizia
L
Molecular Biology Section, Department of Biochemistry and Molecular Biology, Ferrara University, Via Fossato di Mortara, 74, Ferrara, 44100, Italy.
Pocaterra
Barbara
B
Tavanti
Elisa
E
Lambertini
Elisabetta
E
Vesce
Fortunato
F
Gambari
Roberto
R
Piva
Roberta
R
D017209:Apoptosis / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D053148:Caspase 3 / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D011247:Pregnancy; D053245:RANK Ligand / Q000096:biosynthesis; D014162:Transfection; D019014:fas Receptor / Q000096:biosynthesis
D047628:Estrogen Receptor alpha; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D019014:fas Receptor; D016173:Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; D053148:Caspase 3