CCAAT/enhancer binding protein β-deficiency enhances type 1 diabetic bone phenotype by increasing marrow adiposity and bone resorption

• DOI: 10.1152/ajpregu.00764.2010
• Publication Date: 2011-02-24T05:35:58Z
• Authors: Katherine J. Motyl; Michelle Raetz; Srinivasan Arjun ...; Richard C. Schwartz; Laura R. McCabe
• Keywords: Blood Glucose; Male; Mice, Knockout; 0301 basic medicine; Analysis of Variance; Osteoblasts; Genotype; CCAAT-Enhancer-Binding Protein-beta; Biomechanical Phenomena; Diabetes Mellitus, Experimental; Diabetes Complications; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Diabetes Mellitus, Type 1; Gene Expression Regulation; Bone Density; Bone Marrow; Animals; Femur; Bone Resorption; Adiposity

Bone loss in type 1 diabetes is accompanied by increased marrow fat, which could directly reduce osteoblast activity or result from altered bone mesenchymal cell lineage selection (adipocyte vs. osteoblast). CCAAT/enhancer binding protein beta (C/EBPβ) an important regulator of both adipocyte and differentiation. C/EBPβ-null mice have delayed formation defective lipid accumulation brown adipose tissue. To examine the balance C/EBPβ functions diabetic context, we induced (knockout, KO) mice. We found that deficiency actually enhanced phenotype. While KO had reduced peripheral fat mass compared with wild-type mice, they 5-fold more adipocytes than The adiposity may be attributed to compensation C/EBPδ, peroxisome proliferator-activated receptor-γ2, C/EBPα. Concurrently, observed density. Relative genotype controls, trabecular volume fraction was escalated (-48%) changes (-22%). Despite greater loss, markers were not further suppressed Instead, osteoclast Thus, increases diabetes-induced (not peripheral) depot mass, promotes additional through stimulating resorption. C/EBPβ-deficiency also stiffness exacerbated this (two-way ANOVA P < 0.02). conclude alone responsible for phenotype switch T1 suppression CEBPβ levels decrease increasing