Bone modulation in sustained hematopoietic stimulation in mice.
Bone modulation in sustained hematopoietic stimulation in mice.
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DOI：
10.1182/blood.v77.10.2135.2135
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发表时间：
1991-05
期刊：
影响因子：
20.3
通讯作者：
Minako Y. Lee;R. Fukunaga;Theodore Lee;J. Lottsfeldt;Shigekazu Nagata
中科院分区：
文献类型：
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作者：
Minako Y. Lee;R. Fukunaga;Theodore Lee;J. Lottsfeldt;Shigekazu Nagata
了解荷瘤动物模型粒细胞增多症中观察到的骨调节和高钙血症的病因，并深入了解持续造血刺激对骨组织的影响，正常小鼠造血和骨组织对长期注射重组人和鼠粒细胞集落刺激因子（G-CSF）、鼠粒细胞-巨噬细胞CSF（GM-CSF）、和人促红细胞生成素进行定量分析。破骨细胞活化估计破骨细胞骨内膜比率，确定股骨切片的形态计量分析。在胫骨的横向磨骨切片上测量骨髓和骨面积。重组小鼠G-CSF引起了与骨髓粒细胞及其祖细胞数量显著增加相关的显著粒细胞增多症，并导致粒细胞生成性骨髓扩展为脂肪骨髓。G-CSF处理小鼠的骨显示骨内膜破骨细胞数量显著增加，髓面积增大，骨厚度减少;表明骨内膜骨吸收。虽然GM-CSF对粒细胞生成几乎没有影响，但它引起腹腔巨噬细胞增加，并诱导与G-CSF治疗中观察到的相似的骨变化。促红细胞生成素刺激的增强的红细胞生成也与骨内膜骨吸收的证据相关。这些生长因子引起的骨变化与高钙血症无关。这些动物研究记录了骨调节在造血的持续刺激中的关联，并暗示了造血生长因子对体内骨骼组织的重要生理作用。
To understand the etiology of bone modulation and hypercalcemia observed in granulocytosis of a tumor-bearing animal model and to gain insight into the implication of sustained hematopoietic stimulation on the bone tissue, in vivo responses of normal mouse hematopoietic and bone tissues to long-term injections of recombinant human and murine granulocyte colony-stimulating factor (G-CSF), murine granulocyte-macrophage CSF (GM-CSF), and human erythropoietin were quantitatively analyzed. Osteoclast activation was estimated by the osteoclast-endosteal ratio, determined by morphometric analyses of femoral sections. Medullary and bone areas were measured on transverse ground bone sections of the tibia. Recombinant murine G-CSF provoked marked granulocytosis associated with significant increases in the number of marrow granulocytes and their progenitors, and caused expansion of granulopoietic marrow into fatty marrow. The bone of G-CSF-treated mice showed a significant increase in endosteal osteoclast numbers with medullary area enlargement and a reduction in the bone thickness; indicative of endosteal bone resorption. Although GM-CSF had little effect on granulopoiesis, it caused peritoneal macrophages to increase and induced similar bone changes as those observed in G-CSF treatment. Enhanced erythropoiesis stimulated by erythropoietin was also associated with evidence of endosteal bone resorption. Bone changes induced by these growth factors were not associated with hypercalcemia. These animal studies document association of bone modulation in sustained stimulation of hematopoiesis, and implicate important physiologic effects of hematopoietic growth factors on skeletal tissue in vivo.