Deficiency of PPARγin Bone Marrow Stromal Cells Does not Prevent High-Fat Diet-Induced Bone Deterioration in Mice

Abstract

Background: Bone marrow osteoblasts and adipocytes are derived from a common mesenchymal stem cell and have a reciprocal relationship. Peroxisome proliferator-activated receptor gamma (PPARγ), a regulator for adipocyte differentiation, may be a potential target for reducing obesity and increasing bone mass. Objectives: This study tested the hypothesis that bone-specific Pparg conditional knockout (cKO), via deletion of Pparg from bone marrow stromal cells (BMSC) using Osterix 1 (Osx1)-Cre, would prevent high-fat (HF) diet-induced bone deterioration in mice. Methods: PPARγcKO (PPARγfl/fl: Osx1-Cre) and floxed littermate control (PPARγfl/fl Osx1-Cre-) mice that were 6 weeks old were randomly assigned to 4 groups (n = 12/group, 6 male and 6 female) and fed ad libitum with either a normal-fat (NF) purified diet (3.85 kcal/g; 10% energy as fat) or an HF diet (4.73 kcal/g; 45% energy as fat) for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured. Data were analyzed by 2-way ANOVA with Tukey post hoc comparison. Results: The HF diet decreased the tibial and lumbar vertebrae trabecular bone volume/total volume (BV/TV) by 28% and 18%, respectively, compared to the NF diet (P < 0.01). PPARγcKO mice had 23% lower body fat mass and 9% lower lean mass than control mice. PPARγcKO mice had 41% greater tibial trabecular BV/TV compared to control mice. None of trabecular bone parameters at the second lumbar vertebra were affected by genotype. PPARγcKO mice had decreased cortical thickness compared to control mice. PPARγcKO mice had a 14% lower (P < 0.01) serum concentration of leptin and a 35% higher (P < 0.05) concentration of osteocalcin compared with control mice. Conclusions: These data indicate that PPARγhas site-specific impacts on bone structures in mice and that knockout PPARγin BMSC increased bone mass (BV/TV) in the tibia but not the lumbar vertebrae. PPARγdisruption in BMSC did not prevent HF diet-induced bone deterioration in mice.