Adrenal steroids modulate osteoblast function during Brucella abortus infection

GENTILINI MV; PESCE VIGLIETTI, AYELÉN IVANA; ARRIOLA BENÍTEZ, PAULA CONSTANZA; IGLESIAS MOLLI, ANDREA ; CERRONE, GLORIA EDITH; GUILLERMO HERNÁN GIAMBARTOLOMEI; MARÍA VICTORIA DELPINO

Congreso; Reunion conjunta de sociedades de biociencias 2017; 2017

ADRENAL STEROIDS MODULATE OSTEOBLAST FUNCTION DURING Brucella abortus INFECTIONBrucella abortus (Ba) induces an inflammatory response that stimulates the endocrine system resulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the most common presentation of the active disease in humans and we have previously demonstrated that Ba infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast (MC3T3-E1) during Ba infection. Our results indicated that DHEA treatment reversed the effect of Ba infection on osteoblast by increasing the proliferation (BrDU, CSFE), cell viability (MTT) and inhibiting osteoblast apoptosis (Annexin V, TUNEL & Hoechst). In contrast, cortisol increased the effect of Ba infection. DHEA, also, reversed the inhibitory effect induced by Ba infection on osteoblast matrix deposition (Alizarin & Sirius Red staining) in an estrogen receptor (antagonist fulvestrant) and ERK1/2 (specific inhibitor PD98059) dependent manner.It is known that cortisol regulates target genes by binding to the glucocorticoid receptor (GR). Ba infection inhibited GR-α and this effect could not be reversed by cortisol or DHEA treatment. Ba did not induce changes in the expression of GR-β. Besides, the capacity of cells to respond to cortisol not only is dependent on GR expression but also on its intracellular bioavailability. The levels of intracellular cortisol is a result of the activity of the isoenzymes 11βHSD1 (cortisone to cortisol conversion), 11β-HSD2 (cortisol to cortisone). Alterations in the expression of these isoenzymes in bone cells are associated with bone loss. Our data showed that Ba infection increased 11β-HSD1 expression. Cortisol treatment inhibited the 11β-HSD1 expression induced by Ba. DHEA treatment had no effect. Ba infection did not induce changes in expression of 11β-HSD2.We conclude that DHEA intervention improve osteoblast function during Ba infection. Thus, DHEA could be considered as a new treatment against osteoarticular brucellosis.