Abstract
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.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Apoptosis / drug effects
- Apoptosis / physiology
- Carrier Proteins / pharmacology
- Caspase 9
- Caspase Inhibitors
- Caspases / drug effects
- Caspases / metabolism
- Cell Survival / drug effects
- Cells, Cultured
- Cysteine Proteinase Inhibitors / pharmacology
- Enzyme Activation / drug effects
- Female
- Macrophage Colony-Stimulating Factor / pharmacology*
- Membrane Glycoproteins / pharmacology
- Mice
- Mice, Inbred ICR
- Oligopeptides / pharmacology
- Osteoclasts / cytology*
- Osteoclasts / drug effects
- Proto-Oncogene Proteins c-bcl-2 / drug effects
- Proto-Oncogene Proteins c-bcl-2 / metabolism*
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Stem Cells / cytology
- Stem Cells / drug effects*
- Up-Regulation
- bcl-X Protein
Substances
- Bcl2l1 protein, mouse
- Carrier Proteins
- Caspase Inhibitors
- Cysteine Proteinase Inhibitors
- Membrane Glycoproteins
- Oligopeptides
- Proto-Oncogene Proteins c-bcl-2
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Tnfrsf11a protein, mouse
- Tnfsf11 protein, mouse
- bcl-X Protein
- benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
- benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone
- Macrophage Colony-Stimulating Factor
- Casp9 protein, mouse
- Caspase 9
- Caspases