Inhibition of PPARγ by bisphenol A diglycidyl ether ameliorates dexamethasone-induced osteoporosis in a mouse model

Abstract

ObjectivesBisphenol A diglycidyl ether (BADGE) is an antagonist for PPARγ that reduces bone marrow adiposity and increases bone formation in some animal models of osteoporosis and osteonecrosis. However, the effect of BADGE treatment on glucocorticoid-induced osteoporosis is unknown. This study investigated the preventive effects of BADGE on steroid-induced osteoporosis in mice.MethodsThirty-six female C57BL/6J mice were randomly divided into normal (phosphate-buffered saline), model (50 mg/kg dexamethasone sodium phosphate [Dex]), and BADGE (30 mg/kg of BADGE, combined with Dex) groups. All groups received intraperitoneal injections of their treatments, daily for 4 weeks. Protein and mRNA expression levels of gene markers were measured. Micro-computed tomography was used to measure physical parameters of femurs. Bone histomorphology was analyzed by hematoxylin and eosin staining. ELISA was used to measure serum osteocalcin and C-terminal telopeptide of type I collagen (CTX-1).ResultsGlucocorticoid treatment enlarged the marrow fat, concomitant with bone deterioration; BADGE treatment reversed steroid-induced marrow adiposity. Compared with the model group, BADGE treatment improved bone quality and increased bone volume, while increasing osteogenic markers and reducing adipogenic markers at both mRNA and protein levels; moreover, it reduced serum CTX-1 and increased serum osteocalcin.ConclusionBADGE treatment ameliorates glucocorticoid-induced osteoporosis by inhibiting PPARγ.