Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-X(L).
Macrophage colony-stimulating factor (M-CSF) is known as one of the factors essential for osteoclast development. In the present study, we examined effects of M-CSF on the apoptotic pathway of osteoclast precursors and their underlying molecular mechanisms. Osteoclast precursors underwent apoptosis in the absence of M-CSF, even in the presence of receptor activator of NF-kappakB ligand (RANKL). Active caspase-3 and -9 were detected in the osteoclast precursors and treatments of precursors with their specific inhibitors (Z-DEVD-FMK and Z-LEHD-FMK) decreased the apoptosis. M-CSF decreased apoptosis in a dose-dependent manner with decreasing in active caspases-3 and -9 levels and up-regulating Bcl-X(L). Those effects of M-CSF on inhibiting apoptosis of osteoclasts precursor by regulating anti-apoptotic signals was more effective when combined with RANKL. These results demonstrate that M-CSF acts as a survival factor for the osteoclast precursors. Furthermore, it is believed that the apoptosis of osteoclast precursors may be involved in the activation of caspase-9 and that M-CSF may promote their survival through Bcl-X(L)-induced inhibition of caspase-9 activation.
Woo
Kyung Mi
KM
College of Dentistry, Kangnung National University, Kangnung 210-702, Korea.
Kim
Hyun-Man
HM
Ko
Jea Seung
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D015854:Up-Regulation; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D051020:bcl-X Protein; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; D016173:Macrophage Colony-Stimulating Factor; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases