This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Botolin, S. Articles by McCabe, L. R. Search for Related Content PubMed PubMed Citation Articles by Botolin, S. Articles by McCabe, L. R.

Increased Bone Adiposity and Peroxisomal Proliferator-Activated Receptor-2 Expression in Type I Diabetic Mice

Departments of Physiology and Radiology (S.B., R.M., L.R.M.), Molecular Imaging Research Center (S.B., R.M., L.R.M.), and Department of Animal Science (M.O.), Michigan State University, East Lansing, Michigan 48824; and Department of Pathology, University of Kentucky (M.-C.F., H.M.), Lexington, Kentucky 40536

Address all correspondence and requests for reprints to: Dr. Laura R. McCabe, Department of Physiology, Michigan State University, 2201 Biomedical Physical Science Building, East Lansing, Michigan 48824. 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. In this study we use a streptozotocin-induced diabetic mouse model to examine the effect of type I diabetes on bone. Histology and microcomputed 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, because resorption markers (tartrate-resistant acid phosphatase 5b, urinary deoxypyridinoline excretion, and tartrate-resistant acid phosphatase 5 mRNA) are unchanged or reduced at 2 and/or 4 wk after diabetes induction. However, osteocalcin mRNA (a marker of late-stage osteoblast differentiation) and dynamic parameters of bone formation were decreased in diabetic tibias, whereas osteoblast number and runx2 and alkaline phosphatase mRNA levels did not differ. These findings suggest that the 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 [peroxisome proliferator-activated receptor 2, resistin, and adipocyte fatty acid binding protein (P2)] 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 IDDM contributes to bone loss through changes in marrow composition resulting in decreased mature osteoblasts and increased adipose accumulation.

This article has been cited by other articles:

				J. L. Fowlkes, R. C. Bunn, L. Liu, E. C. Wahl, H. N. Coleman, G. E. Cockrell, D. S. Perrien, C. K. Lumpkin Jr., and K. M. Thrailkill Runt-Related Transcription Factor 2 (RUNX2) and RUNX2-Related Osteogenic Genes Are Down-Regulated throughout Osteogenesis in Type 1 Diabetes Mellitus Endocrinology, April 1, 2008; 149(4): 1697 - 1704. [Abstract] [Full Text] [PDF]

				C. C. Chuang, R. S. Yang, K. S. Tsai, F. M. Ho, and S. H. Liu Hyperglycemia Enhances Adipogenic Induction of Lipid Accumulation: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2, Phosphoinositide 3-Kinase/Akt, and Peroxisome Proliferator-Activated Receptor {gamma} Signaling Endocrinology, September 1, 2007; 148(9): 4267 - 4275. [Abstract] [Full Text] [PDF]

				B. Lecka-Czernik, C. Ackert-Bicknell, M. L. Adamo, V. Marmolejos, G. A. Churchill, K. R. Shockley, I. R. Reid, A. Grey, and C. J. Rosen Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo Endocrinology, February 1, 2007; 148(2): 903 - 911. [Abstract] [Full Text] [PDF]

				S. Botolin and L. R. McCabe Bone Loss and Increased Bone Adiposity in Spontaneous and Pharmacologically Induced Diabetic Mice Endocrinology, January 1, 2007; 148(1): 198 - 205. [Abstract] [Full Text] [PDF]

				R. Irwin, H. V. Lin, K. J. Motyl, and L. R. McCabe Normal Bone Density Obtained in the Absence of Insulin Receptor Expression in Bone Endocrinology, December 1, 2006; 147(12): 5760 - 5767. [Abstract] [Full Text] [PDF]