Trouillet-Assant Sophie, Gallet Marlène, Nauroy Pauline, Rasigade Jean-Philippe, Flammier Sacha, Parroche Peggy, Marvel Jacqueline, Ferry Tristan, Vandenesch Francois, Jurdic Pierre, Laurent Frederic
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.
Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308 Institut de Génomique Fonctionnelle de Lyon, France.
J Infect Dis. 2015 Feb 15;211(4):571-81. doi: 10.1093/infdis/jiu386. Epub 2014 Jul 8.
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.
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.
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.
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.
骨与关节感染主要由金黄色葡萄球菌引起，与显著的发病率和死亡率相关，其特征为严重炎症和进行性骨破坏。研究大多聚焦于金黄色葡萄球菌与成骨细胞（形成骨基质的细胞）之间的相互作用，而金黄色葡萄球菌与破骨细胞（已知唯一能够降解骨的细胞）之间的相互作用则鲜有研究。
我们建立了原代小鼠破骨细胞的体外感染模型，以研究活的金黄色葡萄球菌对破骨细胞生成和破骨细胞吸收活性的直接影响。
骨髓来源的破骨细胞前体的葡萄球菌感染诱导它们分化为活跃分泌促炎细胞因子的活化巨噬细胞。这些细胞因子增强了未感染的成熟破骨细胞的骨吸收能力，并促进了感染部位未感染的前体的破骨细胞生成。此外，活的金黄色葡萄球菌对成熟破骨细胞的感染通过促进细胞融合直接增强了它们的骨吸收能力。
我们的结果突出了骨与关节感染期间骨质流失所涉及的两种互补机制，表明破骨细胞可能是限制骨破坏的关键靶点。
