Circulating and skeletal insulin-like growth factor-I (IGF-I) concentrations in two inbred strains of mice with different bone mineral densities [see comments]
Recent work has demonstrated differences in femoral bone mineral density between two common inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), across a wide age range. To investigate one possible mechanism that could affect acquisition and maintenance of bone mass in mice, we studied circulatory and skeletal insulin-like growth factor-I (IGF-I) and femoral bone mineral density (F-BMD) by pQCT in C3H and B6 progenitor strains, as well as serum IGF-I obtained from matings between these two strains and mice bred from subsequent F1 intercrosses (F2). Serum IGF-I measured by radioimmunoassay was more than 35% higher in virgin progenitor C3H than virgin B6 at 1, 4, 8, and 10 months of age, and in 8-month-old C3H compared with B6 retired breeders (p \u3c 0.001). In the progenitors, there was also a strong correlation between serum IGF-I and serum alkaline phosphatase (r = 0.51, p = 0.001). In the 4 month F1 females IGF-I levels and F-BMD were intermediate between C3H and B6 progenitors. In contrast, groups of F2 mice with the highest or lowest BMD also had the highest or lowest serum IGF-I (p = 0.0001). IGF-I accounted for \u3e 35% of the variance in F-BMD among the F2 mice. Conditioned media from newborn C3H calvarial cultures had higher concentrations of IGF-I than media from B6 cultures, and cell layer extracts from C3H calvariae exhibited greater alkaline phosphatase activity than cultures from B6 calvarial cells (p \u3c 0.0001). The skeletal content of IGF-I in C3H tibiae, femorae, and calvariae (6-14 weeks of age) was also significantly higher than IGF-I content in the same bones of the B6 mice (p \u3c 0.05). These data suggest that a possible mechanism for the difference in acquisition and maintenance of bone mass between these two inbred strains is related to systemic and skeletal IGF-I synthesis
