Endocrine modulation of Brucella abortus-infected osteocytes function and osteoclastogenesis via modulation of RANKL/OPG

AYELÉN IVANA PESCE VIGLIETTI; GUILLERMO HERNÁN GIAMBARTOLOMEI; MARÍA VICTORIA DELPINO

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

1286-4579

Osteoarticular brucellosis is the most frequent complication of active disease. A large amount of cellsin bone are osteocytes. Since bone remodeling process is regulated by hormones we sought to studythe effect of cortisol and DHEA in Brucella abortus-infected osteocytes. Cortisol treatment inhibited theexpression of IL-6, TNF-a, MMP-2 and RANKL in B. abortus-infected osteocytes. DHEA could reverse theinhibitory effect of cortisol on MMP-2 production. B. abortus infection inhibited connexin 43 (Cx43)expression in osteocytes. This expression was increased when cortisol was incorporated during theinfection and DHEA treatment partially reversed the effect of cortisol. Osteocytes-infected withB. abortus induced osteoclast´s differentiation. Yet, the presence of cortisol, but not DHEA, duringosteocyte infection inhibited osteoclastogenesis. Glucocorticoid receptor (GR) is implicated in thesignaling of cortisol. Infection with B. abortus was able to increase GRa/b ratio. Levels of intracellularcortisol are not only dependent on GR expression but also a result of the activity of the isoenzymes11b-hydroxysteroid dehydrogenase (11b-HSD)-1 (cortisone to cortisol conversion), 11b-HSD2 (cortisolto cortisone conversion). B. abortus infection increased 11b-HSD 1/2 ratio and cortisone mimicked theeffect of cortisol. Our results indicated that cortisol and DHEA could modulate osteocyte responsesduring B. abortus infection