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KMID : 0620920020340050340
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Experimental & Molecular Medicine
2002 Volume.34 No. 5 p.340 ~ p.346
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Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-XL
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Jea Seung Ko/Kyung Mi Woo
Hyun Man Kim/Jea Seung Ko
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Abstract
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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.
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KEYWORD
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apoptosis, bone and bones, caspase, macrophage colony-stimulating factor, osteoclast,
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