B. abortus invasion of osteocyte modulates connexin 43 and integrins expression and induces osteoclastogenesis via RANKL and TNF-α secretion

PESCE VIGLIETTI AI; ARRIOLA BENITEZ PC; GENTILINI MV; VELÁSQUEZ LN; FOSSATI CA; GIAMBARTOLOMEI GH; DELPINO MV

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2015 p. 11 - 20

0019-9567

Osteoarticular brucellosis is the most commonlocalization of human active disease. Osteocytes are the most abundant cells ofbone. They secrete factors that regulate the differentiation of bothosteoblasts and osteoclasts during bone remodeling. The aim of this study is todetermine if Brucella abortus infection modifies osteocyte function. Ourresults indicate that B. abortus infection induced matrix metalloproteinase 2(MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatorycytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. Inaddition, supernatants from B. abortus-infected osteocytes induced bonemarrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizingantibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin(OPG), RANKL´s decoy receptor, we determined that TNF-α and RANKL are involvedin osteoclastogenesis induced by supernatants from B. abortus-infectedosteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α,integrin-β, and CD44 are involved in cell-cell interactions necessary forosteocyte survival. B. abortus infection inhibited the expression of Cx43 butdid not modify the expression of integrins. Yet the expression of both Cx43 andintegrins was inhibited by supernatants from B. abortus-infected macrophages.B. abortus infection was not capable of inducing osteocyte apoptosis. However,supernatants from B. abortus-infected macrophages induced osteocyte apoptosis ina dose-dependent manner. Taken together, our results indicate that B. abortusinfection could alter osteocyte function, contributing to bone damage.