| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Musculoskeletal Diseases Center, JLP Veterans Administration Medical Center, 11201 Benton St, Loma Linda, California 92357, USA
2 Departments of Medicine,
3 Biochemistry and
4 Physiology, Loma Linda University, Loma Linda, California 92354, USA
(Requests for offprints should be addressed to S Mohan; Email: Subburaman.Mohan{at}med.va.gov)
Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/–) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/– mice (n=18–20 per group). Serum IGF-I was decreased by 23% (P<0.001) in mice with IGF-I haploinsufficiency (+/–) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0.001) and 12% respectively in the IGF-I (+/–) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0.01) and total volumetric BMD (5%, P<0.05) were decreased significantly in the +/– group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0.55) and periosteal circumference (r=0.66) in the pooled data from the +/+ and +/– groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population.
This article has been cited by other articles:
|
|
 |
|
  K. E. Govoni, J. E. Wergedal, R. B. Chadwick, A. K. Srivastava, and S. Mohan Prepubertal OVX increases IGF-I expression and bone accretion in C57BL/6J mice Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1172 - E1180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. DeMambro, D. R. Clemmons, L. G. Horton, M. L. Bouxsein, T. L. Wood, W. G. Beamer, E. Canalis, and C. J. Rosen Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice Endocrinology, May 1, 2008; 149(5): 2051 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Govoni, J. E. Wergedal, L. Florin, P. Angel, D. J. Baylink, and S. Mohan Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion Endocrinology, December 1, 2007; 148(12): 5706 - 5715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Govoni, S. K. Lee, Y.-S. Chung, R. R. Behringer, J. E. Wergedal, D. J. Baylink, and S. Mohan Disruption of insulin-like growth factor-I expression in type II{alpha}I collagen-expressing cells reduces bone length and width in mice Physiol Genomics, August 20, 2007; 30(3): 354 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Davey and H. E. MacLean Current and future approaches using genetically modified mice in endocrine research Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E429 - E438. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
