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Journal of Diabetes Research
Volume 2014, Article ID 703589, 9 pages
Research Article

Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone

1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
2Arkansas Children’s Hospital, 1 Children’s Way, Slot 512-6, Little Rock, AR 72202, USA
3Arkansas Children’s Hospital Research Institute, Little Rock, AR, USA
4Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
5Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA
6VA Tennessee Valley Health Care System, Vanderbilt University Medical Center, Nashville, TN, USA
7Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA
8Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA

Received 7 February 2014; Accepted 30 April 2014; Published 18 May 2014

Academic Editor: Md. Shahidul Islam

Copyright © 2014 Kathryn Thrailkill et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.