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Submitted on December 30, 2004
Accepted on May 10, 2005
2 expression in type I diabetic mice
Michigan State University, Departments of Physiology and Radiology, Molecular, Imaging Research Center, Department of Animal Science, University of Kentucky, Department of Pathology
* To whom correspondence should be addressed. E-mail: mccabel{at}msu.edu.
Decreased bone mass, osteoporosis and increased fracture rates are common skeletal complications in patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes). IDDM develops from little or no insulin production and is marked by elevated blood glucose levels and weight loss. Here we use a streptozotocin-induced diabetic mouse model to examine the effect of type I diabetes on bone. Histology and micro-computed tomography demonstrate that adult diabetic mice, exhibiting increased plasma glucose and osmolality, have decreased trabecular bone mineral content compared with controls. Bone resorption could not completely account for this effect as resorption markers (tartrate resistant acid phosphatase (TRAP) 5b, urine deoxypyridinoline (DPD) excretion, TRAP5 mRNA) are unchanged or reduced at 2 and/or 4 weeks post-diabetes induction. However, osteocalcin mRNA (a marker of late stage osteoblast differentiation) and dynamic parameters of bone formation were decreased in diabetic tibias, while osteoblast number and runx2 and alkaline phosphatase mRNA levels did not differ. These findings suggest that final stages of osteoblast maturation and function are suppressed. We also propose a second mechanism contributing to diabetic bone loss: increased marrow adiposity. This is supported by increased expression of adipocyte markers (PPAR
2, resistin and aP2) and the appearance of lipid dense adipocytes in diabetic tibias. In contrast to bone marrow, adipose stores at other sites are depleted in diabetic mice as indicated by decreased body, liver and peripheral adipose tissue weights. These findings suggest that type I diabetes contributes to bone loss through changes in marrow composition resulting in decreased mature osteoblasts and increased adipose accumulation.
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