Systemic injection of FGF-2 stimulates endocortical bone modelling in SAMP6, a murine model of low turnover osteopenia.
The effects of systemically administered fibroblast growth factor-2 (FGF-2) at doses of 0.1 and 0.3 mg/kg/day for 7 days were investigated 5-week-old male SAMP6 mice, a model of low turnover osteopenia. The bone histomorphometry in the distal epiphyseal growth plate of the femur showed that 0.3 mg/kg/day of FGF-2 decreased the longitudinal growth rate and cartilage cell production rate and increased the growth plate width. Growth plate chondrocytes showed the features of defective endochondral ossification at the same dosage level. In the distal one third of the femur, the marrow trabecular area, endocortical mineral apposition rate and/or bone formation rate were increased in both the SAMP6 mice given 0.1 and 0.3 mg of FGF-2/kg/day. In this region, the endocortical osteoblasts were hypertrophied with some layers of overlying proliferated fibroblastic mesenchymal cells. The presence of small foci of bone formation within the layers of these mesenchymal cells indicates their osteogenic potential. On the other hand, the periosteal bone formation rate in the mid-shaft of the femur was depressed in the 0.3 mg/kg/day group. These results suggest that systemically administered FGF-2 may have the possibility to increase the peak bone mass in SAMP6 by stimulating the osteoprogenitor cells to proliferate and differentiate into osteoblasts and enhancing endocortical bone modelling. The higher dose of FGF-2, however, inhibited both endochondral and periosteal bone formation.
Nagai
H
H
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Tsukuda
R
R
Yamasaki
H
H
Mayahara
H
H
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D016723:Bone Remodeling / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2