Disruption of insulin-like growth factor-I expression in type IIαI 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, typeII alpha I-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 II alpha I regulates bone accretion that occurs during postnatal growth period.