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I collagen expressing cells reduces bone length and width in mice
1 Musculoskeletal Disease Center, Jerry L. Pettis VA Medical Center, Loma Linda, California, United States
2 Cancer Center, MD Anderson Cancer Center, Houston, Texas, United States
3 Musculoskeletal Disease Center, Jerry L. Pettis VA Medical Center and Loma Linda University, Loma Linda, California, United States
4 Loma Linda University, Loma Linda, California, United States
* To whom correspondence should be addressed. E-mail: subburaman.mohan{at}med.va.gov.
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 versus 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
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 weeks of age and peripheral quantitative computed tomography at 12 weeks of age. Body length, areal BMD, and bone mineral content (BMC) were reduced (P < 0.05) between 4 and 12 weeks in the conditional mutant mice. Bone width was reduced 7% in the vertebrae and femur (P < 0.05) of conditional mutant mice at 12 weeks. 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 weeks 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 (BP)-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 (R), IGF-IR, and IGFBP-3 expression were observed (P 
0.20). In conclusion, IGF-I from cells expressing procollagen, typeIII regulates bone accretion that occurs during postnatal growth period.
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