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

AYELÉN IVANA PESCE VIGLIETTI; PAULA CONSTANZA ARRIOLA BENITEZ; MARÍA VIRGINIA GENTILINI; LIS NOELIA VELASQUEZ; CARLOS FOSSATI; GUILLERMO HERNÁN GIAMBARTOLOMEI; MARÍA VICTORIA DELPINO

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2015

0019-9567

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblast and osteoclast during bone remodeling. The aim of this study is to determine if Brucella abortus infection modifies osteocyte function. Our results indicate that B. abortus infection induced matrix metalloproteinase(MMP)-2, receptor activator for nuclear factor κ B ligand (RANKL), proinflamatory cytokines and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants from B. abortus-infected osteocytes induced bone marrow derived monocytes (BMM) to undergo osteoclastogenesis. Using a neutralizing antibodies against tumor necrosis factor (TNF)-α or osteoprotegerin (OPG), RANKL?s decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants from B. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β and CD44 all of them involved in cell-cell interactions are necessary for osteocyte survival. B. abortus infection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet, the expression of both Cx43 and integrins was inhibited by supernatants from B. abortus-infected macrophages. B. abortus infection was not capable to induce osteocyte apoptosis. However supernatants from B. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taking together our results indicate that B. abortus infection could alter osteocyte function contributing to bone damage.