Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-XL.
- Author:
Kyung Mi WOO
1
;
Hyun Man KIM
;
Jea Seung KO
Author Information
1. College of Dentistry, Kangnung National University, Kangung, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
bone and bones;
caspases;
macrophage colony-stimulating factor;
osteoclast
- MeSH:
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
- From:Experimental & Molecular Medicine
2002;34(5):340-346
- CountryRepublic of Korea
- Language:English
-
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.
