Faculty Research 1990 - 1999

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

Document Type

Article

Publication Date

1997

Keywords

Alkaline-Phosphatase: bl, me, Animal, Bone-Density, Female, Femur, Insulin-Like-Growth-Factor-I: me, Mice, Mice-Inbred-C3H, Mice-Inbred-C57BL, Radioimmunoassay, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S

First Page

217

Last Page

223

JAX Source

Bone 1997 Sep;21(3):217-23

Grant

AG109420451/AG/NIA, AR43618/AR/NIAMS, CA34196/CA/NCI

Abstract

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 < 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 > 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 < 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.

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