Dexamethasone treatment alters function of adipocytes from a mesenchymal stromal cell line

Abstract

Osteoporosis and osteonecrosis are associated with corticosteroid treatment, but the pathophysiologies are unclear. We hypothesized that mature adipocytes present within the bone marrow compartment play a key role in the development of both diseases. Adipocytes have recognized regulatory effects on bone viability and healing by releasing signaling molecules called adipokines. Our purpose was to evaluate whether dexamethasone alters adipokine expression in differentiated bone-marrow-derived adipocytes. Adipocytes differentiated from mouse D1 mesenchymal stromal cells were treated with dexamethasone (10−5, 10−6, 10−7, or 10−8M) or with diluent alone (controls) for up to 6days. Using real-time polymerase chain reaction and enzyme-linked immunosorbent assay analyses, six key adipokines and the transcription factor HIF-1α were evaluated. Dexamethasone treatment increased PAI-1 protein expression with increased mRNA expression at 4days, while decreasing HIF-1α mRNA expression and protein concentrations. VEGF A mRNA expression was increased at 4days for most dexamethasone concentrations, with minimal changes in protein levels. Dexamethasone increased adiponectin mRNA expression and protein levels at 4 and 6days and decreased leptin, interleukin-6, and tumor necrosis factor α mRNA expression at all time periods. Dexamethasone treatment of bone-marrow-derived adipocytes resulted in detectable changes in mRNA expression and protein levels of adipokines and HIF-1α. The detected adipokine alterations could be important early events in the pathogenesis of steroid-induced osteonecrosis and osteoporosis.