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.

中文翻译：

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巨噬细胞集落刺激因子通过上调Bcl-X（L）来促进破骨细胞前体的存活。

巨噬细胞集落刺激因子（M-CSF）被称为破骨细胞发育必不可少的因子之一。在本研究中，我们检查了M-CSF对破骨细胞前体细胞凋亡途径及其潜在分子机制的影响。在没有M-CSF的情况下，甚至在存在NF-κB配体的受体激活剂（RANKL）的情况下，破骨细胞前体也会发生凋亡。在破骨细胞前体中检测到有活性的caspase-3和-9，用其特异性抑制剂（Z-DEVD-FMK和Z-LEHD-FMK）处理前体可降低细胞凋亡。M-CSF以剂量依赖的方式减少细胞凋亡，同时降低活跃的caspases-3和-9水平并上调Bcl-X（L）。当与RANKL联合使用时，M-CSF通过调节抗凋亡信号抑制破骨细胞前体细胞凋亡的那些作用更为有效。这些结果证明M-CSF充当破骨细胞前体的存活因子。此外，据信破骨细胞前体的凋亡可能与caspase-9的激活有关，M-CSF可能通过Bcl-X（L）诱导的caspase-9激活的抑制来促进其存活。