Granulocyte Colony-Stimulating Factor Induces Osteoblast Apoptosis and Inhibits Osteoblast Differentiation
Granulocyte Colony-Stimulating Factor Induces Osteoblast Apoptosis and Inhibits Osteoblast Differentiation
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DOI：
10.1359/jbmr.080612
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发表时间：
2008-11-01
影响因子：
6.2
通讯作者：
Link, Daniel C.
中科院分区：
文献类型：
--
作者：
Christopher, Matthew J.;Link, Daniel C.
粒细胞集落刺激因子（G-CSF）长期治疗小鼠或人与临床显著的破骨细胞活性和数量增加的骨质减少有关。此外。最近的报道已经观察到G-CSF给药期间成熟成骨细胞数量的减少。然而，G-CSF对成骨细胞室的抑制作用程度及其机制尚不清楚。在此，我们表明短期G-CSF治疗小鼠导致骨内膜和骨小梁成骨细胞数量减少。这种作用只对成熟的成骨细胞有效，因为骨细化细胞，骨细胞。而骨膜成骨细胞则不受影响。g - csf通过诱导成骨细胞凋亡加速骨髓成骨细胞的更新。此外，虽然G-CSF治疗能显著增加成骨细胞的数量，但成熟成骨细胞的分化受到损害。骨髓移植研究表明，G-CSF通过造血中介作用抑制成骨细胞。最后，G-CSF治疗通过抑制成熟成骨细胞，也导致骨髓中骨保护素表达显著下降，而RANKL的表达保持相对稳定，提示长期G-CSF治疗导致破骨细胞生成增加的新机制。在苗条。这些发现提示造血系统可能在G-CSF治疗过程中调控成骨细胞分化和凋亡中发挥新的作用。
Long-term treatment of mice Or humans with granulocyte colony-stimulating factor (G-CSF) is associated with a clinically significant osteopenia characterized by increased osteoclast activity and number. In addition. recent reports have observed a decrease in number of mature osteoblasts during G-CSF administration. However, neither the extent of G-CSF's suppressive effect on the osteoblast compartment nor its mechanisms are well understood. Herein, we show that short-term G-CSF treatment in mice leads to decreased numbers of endosteal and trabecular osteoblasts. The effect is specific to mature osteoblasts, because bone-fining cells, osteocytes. and periosteal osteoblasts are unaffected. G-CSF treatment accelerates osteoblast turnover the bone marrow by Inducing g osteoblast apoptosis. In addition, whereas G-CSF treatment sharply increases osteoprogenitor number, differentiation of mature osteoblasts is impaired. Bone marrow transplantation studies show that G-CSF acts through a hematopoietic intermediary to suppress osteoblasts. Finally, G-CSF treatment, through suppression of mature osteoblasts, also leads to a marked decrease in osteoprotegerin expression in the bone marrow, whereas expression of RANKL remains relatively constant, suggesting a novel mechanism contributing to the increased osteoclastogenesis seen with long-term G-CSF treatment. In SLIM. these findings suggest that the hematopoietic system may play a novel role in regulating osteoblast differentiation and apoptosis during G-CSF treatment.