Circulating and skeletal insulin-like growth factor-I (IGF-i) concentrations in two inbred strains of mice with different bone mineral densities

• Published in: Bone (New York, N.Y.) N.Y.), 1997-09, Vol.21 (3), p.217-223
• Main Authors: Rosen, C.J., Dimai, H.P., Vereault, D., Donahue, L.R., Beamer, W.G., Farley, J., Linkhart, S., Linkhart, T., Mohan, S., Baylink, D.J.
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Alkaline Phosphatase - blood; Alkaline Phosphatase - metabolism; Animals; Biological and medical sciences; Bone Density; Female; Femoral bone density; Femur; Fundamental and applied biological sciences. Psychology; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Radioimmunoassay; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/S8756-3282(97)00143-9

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 F 1 intercrosses (F 2). 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 < 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 F 1 females IGF-I levels and F-BMD were intermediate between C3H and B6 progenitors. In contrast, groups of F 2 mice with the highest or lowest BMD also had the highest or lowest serum IGF-I ( p = 0.0001). IGF-I accounted for >35% of the variance in F-BMD among the F 2 mice. Conditioned media from newborn C3H calvarial cultures has 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 < 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 < 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.