Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice.
It is well established that insulin-like growth factor (IGF)-I is critical for the regulation of peak bone mineral density (BMD) and bone width. However, the role of systemic vs. local IGF-I is not well understood. To determine the role local IGF-I plays in regulating BMD and bone width, we crossed IGF-I flox/flox mice with procollagen, typeIIalphaI-Cre mice to generate conditional mutants in which chondrocyte-derived IGF-I was disrupted. Bone parameters were measured by dual X-ray absorptiometry at 2, 4, 8, and 12 wk of age and peripheral quantitative computed tomography at 12 wk of age. Body length, areal BMD, and bone mineral content (BMC) were reduced (P < 0.05) between 4 and 12 wk in the conditional mutant mice. Bone width was reduced 7% in the vertebrae and femur (P < 0.05) of conditional mutant mice at 12 wk. Gains in body length and total body BMC and BMD were reduced by 27, 22, and 18%, respectively (P < 0.05) in conditional mutant mice between 2 and 4 wk of age. Expression of parathyroid hormone related protein, parathyroid hormone receptor, distal-less homeobox (Dlx)-5, SRY-box containing gene-9, and IGF binding protein (IGFBP)-5 were reduced 27, 36, 45, 33, and 45%, respectively, in the conditional mutant cartilage (P < 0.05); however, no changes in Indian hedgehog, Dlx-3, growth hormone receptor, IGF-I receptor, and IGFBP-3 expression were observed (P > or = 0.20). In conclusion, IGF-I from cells expressing procollagen type IIalphaI regulates bone accretion that occurs during postnatal growth period.
Govoni
Kristen E
KE
Jerry L. Pettis Veterans Affairs Medical Center and Loma Linda University, Loma Linda, California 92357, USA.
Lee
Seong Keun
SK
Chung
Yoon-Sok
YS
Behringer
Richard R
RR
Wergedal
Jon E
JE
Baylink
David J
DJ
Mohan
Subburaman
S
D000818:Animals; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology; D024043:Collagen Type II / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis
C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I