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Inhibition of PPARγ prevents type I diabetic bone marrow adiposity but not bone loss
Author(s) -
Botolin Sergiu,
McCabe Laura R.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20804
Subject(s) - endocrinology , medicine , osteocalcin , osteoblast , type 2 diabetes , bone marrow , diabetes mellitus , adipocyte , adipose tissue , chemistry , alkaline phosphatase , in vitro , biochemistry , enzyme
Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin‐deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator‐activated receptor γ (PPARγ) antagonist, bisphenol‐A‐diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes‐associated hyperglycemia or weight loss, but did prevent diabetes‐induced hyperlipidemia and effectively blocked diabetes type I‐induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro‐computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype. J. Cell. Physiol. 209: 967–976, 2006. © 2006 Wiley‐Liss, Inc.