Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms.
Document Type
Article
Publication Date
2003
Keywords
Bone-Density, Densitometry-X-Ray, Female, Femur, Growth-Hormone, Insulin-Like-Growth-Factor-I, Insulin-Like-Growth-Factor-II, Male, Mice, Mice-Inbred-C57BL, Mice-Knockout, Mutation, Organ-Weight, Osteocalcin, Sex-Characteristics, Sex-Maturation, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S, Tomography-X-Ray-Computed
First Page
929
Last Page
936
JAX Source
Endocrinology 2003 Mar; 144(3):929-36.
Abstract
To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25-40%, 15-17%, and 8-10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40-55%, 11-18%, and 25-32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms.
Recommended Citation
Mohan S,
Richman C,
Guo R,
Amaar Y,
Donahue LR,
Wergedal J,
Baylink DJ.
Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms. Endocrinology 2003 Mar; 144(3):929-36.