ADRENAL STEROIDS MODULATE OSTEOBLAST FUNCTION DURING Brucella abortus INFECTION

MARÍA VIRGINIA GENTILINI; AYELÉN IVANA PESCE VIGLIETTI; ANDREA MOLLI; GLORIA CERRONE; GUILLERMO HERNÁN GIAMBARTOLOMEI; MARÍA VICTORIA DELPINO

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Brucella abortus (Ba) induces an inflammatory response that stimulates theendocrine system resulting in the secretion of cortisol anddehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the mostcommon presentation of the active disease in humans and we have previouslydemonstrated that Ba infection inhibits osteoblast function. We aimed toevaluate the role of cortisol and DHEA on osteoblast (MC3T3-E1) during Bainfection. Our results indicated that DHEA treatment reversed the effect of Bainfection on osteoblast by increasing the proliferation (BrDU, CSFE), cellviability (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 theglucocorticoid receptor (GR). Ba infection inhibited GR-α and this effect couldnot be reversed by cortisol or DHEA treatment. Ba did not induce changes inthe 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 associatedwith bone loss. Our data showed that Ba infection increased 11β-HSD1expression. Cortisol treatment inhibited the 11β-HSD1 expression induced byBa. DHEA treatment had no effect. Ba infection did not induce changes inexpression of 11β-HSD2.We conclude that DHEA intervention improve osteoblast function duringBa infection. Thus, DHEA could be considered as a new treatment againstosteoarticular brucellosis.