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

PESCE VIGLIETTI AYELÉN; ARRIOLA BENITEZ PAULA C; GENTILINI M. VIRGINIA; VELAZQUEZ LIS NOELIA; C. ALBERTO FOSSATI; GIAMBARTOLOMEI GH; DELPINO M. VICTORIA

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016

0019-9567

Osteoarticularbrucellosis is the most common localization of human active disease. Osteocytes are the mostabundant cells of bone. They secretefactors that regulate the differentiationofbothosteoblast and osteoclast during bone remodeling. The aim of this study is to determine if Brucella abortus infection modifies osteocytefunction. Our results indicate that B.abortus infection induced matrix metalloproteinase (MMP)-2, receptor activator for nuclearfactor κ B ligand (RANKL), proinflamatory cytokines and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants from B. abortus-infected osteocytes induced bone marrow derivedmonocytes (BMM) to undergo osteoclastogenesis. Using a neutralizing antibodiesagainst tumor necrosis factor (TNF)-α or osteoprotegerin (OPG), RANKL?s decoyreceptor, we determined that TNF-α and RANKL are involved in osteoclastogenesisinduced 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. abortusinfection inhibited the expression of Cx43 but did not modify the expression ofintegrins. Yet, the expression of both Cx43 and integrins was inhibited bysupernatants from B. abortus-infectedmacrophages. B. abortus infection wasnot capable to induce osteocyte apoptosis. However supernatants from B. abortus-infected macrophages inducedosteocyte apoptosis in a dose-dependent manner. Taking together our resultsindicate that B. abortus infectioncould alter osteocyte function contributing to bone damage.