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J Infect Dis. 2015 Feb 15;211(4):571-81. doi: 10.1093/infdis/jiu386. Epub 2014 Jul 8.

Dual impact of live Staphylococcus aureus on the osteoclast lineage, leading to increased bone resorption.

Author information

1
Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
2
Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308 Institut de Génomique Fonctionnelle de Lyon, France.
3
CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.

Abstract

BACKGROUND:

Bone and joint infection, mainly caused by Staphylococcus aureus, is associated with significant morbidity and mortality, characterized by severe inflammation and progressive bone destruction. Studies mostly focused on the interaction between S. aureus and osteoblasts, the bone matrix-forming cells, while interactions between S. aureus and osteoclasts, the only cells known to be able to degrade bone, have been poorly explored.

METHODS:

We developed an in vitro infection model of primary murine osteoclasts to study the direct impact of live S. aureus on osteoclastogenesis and osteoclast resorption activity.

RESULTS:

Staphylococcal infection of bone marrow-derived osteoclast precursors induced their differentiation into activated macrophages that actively secreted proinflammatory cytokines. These cytokines enhanced the bone resorption capacity of uninfected mature osteoclasts and promoted osteoclastogenesis of the uninfected precursors at the site of infection. Moreover, infection of mature osteoclasts by live S. aureus directly enhanced their ability to resorb bone by promoting cellular fusion.

CONCLUSIONS:

Our results highlighted two complementary mechanisms involved in bone loss during bone and joint infection, suggesting that osteoclasts could be a pivotal target for limiting bone destruction.

KEYWORDS:

Staphylococcus aureus; bone and joint infections; osteoclastogenesis; resorption

PMID:
25006047
DOI:
10.1093/infdis/jiu386
[Indexed for MEDLINE]

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