Differences in bone responses to recombinant human granulocyte colony-stimulating factor between mice and rats.

ABSTRACT

The authors previously demonstrated that high doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) induce bone changes characterized by accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification in rats. As a basis for future analysis of the mechanisms of rhG-CSF-induced bone changes, the present study was undertaken to determine whether the bone changes observed in rats are also induced in mice. The experiment was conducted under the conditions that clearly induce bone changes in rats. Namely, 4- or 6-week-old mice received a subcutaneous injection of rhG-CSF (1,000 or 5,000 microg/kg) for 14 or 28 days, and then the femur and tibia were evaluated histopathologically. A marked increase in peripheral blood leukocyte counts, prominent splenomegaly, and a marked increase in the number of granulopoietic cells in the bone marrow, all of which are related to the major pharmacological activity of G-CSF, was observed in the rhG-CSF-treated mice. The histopathological changes observed in the rat bone, such as accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification, were not detected in mice. These results suggest that there is a species-related difference between mice and rats in the response of the bone to rhG-CSF treatment, and that the reactivity in mice is lower than in rats.