Merlin functions as a critical regulator in Staphylococcus aureus-induced osteomyelitis,Journal of Cellular Physiology

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Merlin functions as a critical regulator in Staphylococcus aureus-induced osteomyelitis
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-08-11 , DOI: 10.1002/jcp.30550
Zubin Zhou ₁ , Yuanliang Chen ₂ , Hong Sung Min ₁ , Yongbai Wan ₂ , Haojie Shan ₁ , Yiwei Lin ₁ , Wenyang Xia ₁ , Fuli Yin ₁ , Chaolai Jiang ₁ , Xiaowei Yu ₁

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Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus-induced osteomyelitis and its underlying mechanisms. S. aureus-induced osteomyelitis mouse model was established in Merlin^fl/flLyz2^cre/+ and Merlin^fl/flLyz2^+/+ mice. Bone marrow–derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1^fl/fl mice were further crossed with Lyz2-Cre mice to establish myeloid cell conditional knockout mice (DCAF1^fl/flLyz2^cre/+). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus-infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1-Cul4-associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus-induced osteomyelitis through the regulation of DCAF1.

中文翻译：

Merlin 在金黄色葡萄球菌诱导的骨髓炎中起关键调节作用

Merlin 被称为肿瘤抑制因子，而其在骨髓炎中的作用仍不清楚。本研究旨在探讨 Merlin 在金黄色葡萄球菌诱导的骨髓炎中的作用及其潜在机制。^{在 Merlin fl/fl} Lyz2 ^cre/+和 Merlin ^fl/fl Lyz2 ^+/+中建立金黄色葡萄球菌诱导的骨髓炎小鼠模型老鼠。骨髓来源的巨噬细胞 (BMDM) 被脂多糖 (LPS) 分离和刺激。进行生物测定，包括定量逆转录聚合酶链反应 (qRT-PCR)、蛋白质印迹分析和酶联免疫吸附测定，以确定靶基因或蛋白质的水平。应用免疫沉淀来确定蛋白质之间的相互作用。DCAF1 ^fl/fl小鼠进一步与 Lyz2-Cre 小鼠杂交以建立骨髓细胞条件性敲除小鼠 (DCAF1 ^fl/fl Lyz2 ^cre/+ )。发现骨髓炎和金黄色葡萄球菌患者的Merlin水平升高- 感染的 BMDM。巨噬细胞中的 Merlin 缺乏抑制了炎性细胞因子的产生并改善了由金黄色葡萄球菌引起的骨髓炎症状。巨噬细胞中的 Merlin 缺乏也抑制了 LPS 诱导的 BMDM 中促炎细胞因子的产生。Merlin 缺乏对炎症反应的抑制作用与 DDB1-Cul4 相关因子 1 (DCAF1) 相关。总之，Merlin 缺乏通过调节 DCAF1 来改善金黄色葡萄球菌诱导的骨髓炎。

更新日期：2021-08-11

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