Disruption of insulin-like growth factor-I expression in type IIαI collagen-expressing cells reduces bone length and width in mice

KE Govoni, SK Lee, YS Chung… - Physiological …, 2007 - journals.physiology.org
KE Govoni, SK Lee, YS Chung, RR Behringer, JE Wergedal, DJ Baylink, S Mohan
Physiological genomics, 2007journals.physiology.org
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, typeIIαI-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 …
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, typeIIαI-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 ≥ 0.20). In conclusion, IGF-I from cells expressing procollagen type IIαI regulates bone accretion that occurs during postnatal growth period.
American Physiological Society