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

PESCE VIGLIETTI A. I., ARRIOLA BENITEZ P. C., GENTILINI M. V., VELÁSQUEZ L. N., FOSSATI C. A., GIAMBARTOLOMEI G. H., DELPINO M.V

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016 vol. 84 p. 11 - 20

0019-9567

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells ofbone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aimof this study is to determine if Brucella abortus infection modifies osteocyte function. Our results indicate that B. abortus infectioninduced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-B ligand (RANKL), proinflammatory cytokines,and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants from B. abortus-infected osteocytesinduced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumornecrosis factor alpha (TNF-) or osteoprotegerin (OPG), RANKL?s decoy receptor, we determined that TNF- and RANKL areinvolved in osteoclastogenesis induced by supernatants from B. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrinsE11/gp38, integrin-, integrin-, and CD44 are involved in cell-cell interactions necessary for osteocyte survival. B. abortusinfection inhibited the expression of Cx43 but did 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 inducingosteocyte apoptosis. However, supernatants from B. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependentmanner. Taken together, our results indicate that B. abortus infection could alter osteocyte function, contributing tobone damage.