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Bone modulation in sustained hematopoietic stimulation in mice
MY Lee, R Fukunaga, TJ Lee, JL Lottsfeldt and S Nagata
Department of Biological Structure, University of Washington, Seattle
98195.
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.
Volume 77,
Issue 10,
pp. 2135-2141,
05/15/1991
Copyright © 1991 by The American Society of Hematology

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