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The Age-Related Difference in Bone Changes in Rats Induced by Recombinant Human Granulocyte Colony-Stimulating Factor

Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., 14016 Minamihara, Nakaminowa, Minowa-machi, Kamiina-gun, Nagano 339-46, Japan, Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

Yoshiyuki Sakamaki

Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., 14016 Minamihara, Nakaminowa, Minowa-machi, Kamiina-gun, Nagano 339-46, Japan

Akio Miyoshi

Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., 14016 Minamihara, Nakaminowa, Minowa-machi, Kamiina-gun, Nagano 339-46, Japan

Kenji Adachi

Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., 14016 Minamihara, Nakaminowa, Minowa-machi, Kamiina-gun, Nagano 339-46, Japan

Masayoshi Usami

Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., 14016 Minamihara, Nakaminowa, Minowa-machi, Kamiina-gun, Nagano 339-46, Japan

Hiroyuki Nakayama

Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

Kunio Doi

Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

We examined the bone changes in recombinant human granulocyte colony-stimulating factor (rhG-CSF)-treated young and young adult rats in order to investigate the effect of age-related conditions of bone growth on the bone changes induced by rhG-CSF. Recombinant human G-CSF (100 and 1,000 µg/kg/day) was given to rats by daily intravenous injection for 28 days starting at the age of either 6 or 14 wk, and the hindlimb bones were evaluated histopathologically. In the young rats, bone lesions were observed in the 100- and 1,000-µg/kg groups. In the young adult rats, lesions were found only in the 1,000-µg/kg group. The lesions involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification, and there was no age-related difference in these histopathological findings. However, both the incidence of bone involvement and the severity of lesions were greater in the young rats than in the dose-matched young adult rats. The results suggest that the higher dose of rhG-CSF may intrinsically induce bone lesions of a particular histopathological nature in rats regardless of their age, and the action of rhG-CSF on bone may be stronger in young growing rats than in young adults.

Key Words: Cytokines • bone resorption • osteoclasis • osteoclast • bone formation • osteogenesis • intramembranous ossification • histopathology

Toxicologic Pathology, Vol. 25, No. 2, 144-149 (1997)
DOI: 10.1177/019262339702500203


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