Effects of basic fibroblast growth factor (bFGF) on bone formation in growing rats.
The effects of basic fibroblasts growth factor (bFGF) administered intravenously at dosages of 0.1 and 0.3 mg/kg per day for 7 days to growing rats are reported. Static and dynamic histomorphometry techniques were applied to the microradiographs and undecalcified ground sections of the proximal tibiae and tibial shafts. The bone histomorphometric analyses in the proximal tibia revealed that 0.1 mg/kg per day of bFGF increased longitudinal growth rate, cartilage cell production rate, and metaphyseal bone area. In the tibial shaft, the endocortical mineral apposition and bone formation rates, total bone area, total osteoid area, and medullary bone area were increased, but the periosteal mineral apposition and bone formation rates were depressed. Two weeks after the cessation of treatment, the increased osteoid bone on the endocortical surface and in the marrow cavity was completely calcified, and the total mineralized area in the tibial shaft was significantly increased. The rats given 0.3 mg of bFGF/kg per day showed retarded weight gain, defective calcification at the growth plate metaphyseal junction, and on the endocortical surface. The growth plate width was increased, and the longitudinal growth rate, cartilage cell production rate, endocortical labeled surface, and bone formation rate were decreased. Two weeks after the cessation of treatment, these changes were almost reversed, and the longitudinal growth rate and cartilage cell production rate were increased as rebound phenomena. These results suggest that a low dose (0.1 mg/kg per day) of bFGF stimulates endosteal and endochondral bone formation and depresses periosteal bone formation in growing rats.
Nagai
H
H
Drug Safety Research Laboratories, Takeda Chemical Industries Limited, Osaka, Japan.
Tsukuda
R
R
Mayahara
H
H
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects; D007275:Injections, Intravenous; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2