B. abortus modulates osteoblast function through the induction of autophagy

PESCE VIGLIETTI A.I; GENTILINI M. V.; BENITEZ, PAULA CONSTANZA ARRIOLA; GIAMBARTOLOMEI G. H.; DELPINO M. V.

Frontiers in cellular and infection microbiology

Fontiers Media S. A.

Año: 2018

2235-2988

Osteoarticular brucellosis is the most common localization of human active disease.Osteoblasts are specialized mesenchymal-derived cells involved in bone formation andare considered as professional mineralizing cells. Autophagy has been involved inosteoblast metabolism. The present study demonstrates that Brucella abortus infectioninduces the activation of the autophagic pathway in osteoblast cells. Autophagywas revealed by upregulation of LC3II/LC3I ratio and Beclin-1 expression as wellas inhibition of p62 expression in infected cells. Induction of autophagy was alsocorroborated by using the pharmacological inhibitors wortmannin, a PI 3-kinase inhibitor,and leupeptin plus E64 (inhibitors of lysosomal proteases). Autophagy induction create amicroenvironment that modifies osteoblast metabolism by the inhibition of the depositionof organic and mineral matrix, the induction of matrix metalloproteinase (MMP)-2,osteopontin, and RANKL secretion leading to bone loss. Accordingly, autophagy is alsoinvolved in the down-modulation of the master transcription factor in bone formationosterix during B. abortus infection. Taking together our results indicate that B. abortusinduces the activation of autophagy pathway in osteoblast cells and this activation isinvolved in the modulation of osteoblast function and bone formation.