Internalisation of Staphylococcus aureus in osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalised S. aureus in osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor‐focal adhesion kinase (FAK), phosphor‐epidermal growth factor receptor (EGFR) and phosphor‐c‐Src in a time‐dependent way, and blocking EGFR/FAK or c‐Src signalling significantly reduced the internalisation rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalisation in osteoblast and raise the potential of targeting EGFR/FAK and c‐Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis.

中文翻译：

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EGFR/FAK 和 c-Src 信号通路介导成骨细胞对金黄色葡萄球菌的内化。

内在化的金黄色葡萄球菌在成骨细胞起着持久性和骨髓炎复发了至关重要的作用，参与这一过程的机制还不是很清楚。在本研究中，在感染 2 周后，在小鼠血源性骨髓炎的长骨中发现了成骨细胞内化金黄色葡萄球菌的证据。同时，庆大霉素清除细胞外金黄色葡萄球菌可以部分挽救骨丢失，而成骨细胞中残留的细胞内金黄色葡萄球菌可能与持续的骨破坏有关。在成骨细胞 MC3T3 细胞中，细胞内金黄色葡萄球菌早在感染后 15 分钟即可检测到，并且内化率随着感染时间的延长而增加。此外，金黄色葡萄球菌的入侵以时间依赖性方式刺激了磷-粘着斑激酶（FAK）、磷-表皮生长因子受体（EGFR）和磷-c-Src的表达，并阻断了EGFR/FAK或c-Src信号显着降低了成骨细胞中金黄色葡萄球菌的内化率。我们的发现为成骨细胞中金黄色葡萄球菌内化机制提供了新的见解，并提高了靶向 EGFR/FAK 和 c-Src 作为治疗慢性金黄色葡萄球菌骨髓炎的辅助疗法的潜力。