Exp Mol Med.  2002 Nov;34(5):340-346.

Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-XL

• Woo KM
• Kim HM
• Ko JS

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-kB 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-XL. 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-XL-induced inhibition of caspase-9 activation.

Keyword

apoptosis; bone and bones; caspases; macrophage colony-stimulating factor; osteoclast

MeSH Terms

Animals
Apoptosis/drug effects/physiology
Carrier Proteins/pharmacology
Caspases/antagonists & inhibitors/drug effects/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/drug effects
Proto-Oncogene Proteins c-bcl-2/drug effects/*metabolism
Stem Cells/cytology/*drug effects
Up-Regulation