巨噬细胞中的Ddb1- Cul4相关因子1限制了诱导性骨髓炎。
Ddb1-Cullin4-Associated-Factor 1 in Macrophages Restricts the -Induced Osteomyelitis.
作者信息
Zong Yang, Shan Haojie, Yin Fuli, Ma Xin, Jiang Chaolai, Wang Nan, Zhou Lihui, Lin Yiwei, Zhou Zubin, Yu Xiaowei
机构信息
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
出版信息
J Inflamm Res. 2021 Apr 28;14:1667-1676. doi: 10.2147/JIR.S307316. eCollection 2021.
INTRODUCTION
Ddb1-cullin4-associated-factor 1 (DCAF1) is known to regulate protein ubiquitination, while the roles of DCAF1 in osteomyelitis remain unknown. This study aims to investigate the effects of DCAF1 deficiency in macrophages on osteomyelitis and elucidate the molecular mechanism.
METHODS
-induced mouse model of osteomyelitis was established on the DCAF1Lyz2 and DCAF1Lyz2 (control) mice. Flow cytometry was conducted to analyze the populations of adaptive and innate immune cells. Lipopolysaccharides (LPS)-induced bone marrow-derived macrophages (BMDMs) were established. qRT-PCR and immunoblot analysis were used to determine the levels of inflammation-related biomarkers. ELISA was used to determine the release of inflammatory cytokines including IL-1β, IL-6, and TNF.
RESULTS
The populations of immune cells in the bone marrow and spleen were not affected due to DCAF1 deficiency in macrophages. DCAF1 suppressed inflammatory cytokines in LPS-induced BMDMs. Additionally, DCAF1 deficiency in macrophages induced severe symptoms including less bacterial load in the femur, cortical bone loss, and reactive bone formation. Mechanistic study revealed that DCAF1 deficiency induced p38 hyperactivation.
DISCUSSION
DCAF1 in macrophages suppressed the -induced mouse model of osteomyelitis.
引言
已知损伤特异性DNA结合蛋白1-类cullin 4相关因子1（DCAF1）可调节蛋白质泛素化，而DCAF1在骨髓炎中的作用尚不清楚。本研究旨在探讨巨噬细胞中DCAF1缺乏对骨髓炎的影响，并阐明其分子机制。
方法
在DCAF1Lyz2和DCAF1Lyz2（对照）小鼠上建立脂多糖诱导的小鼠骨髓炎模型。进行流式细胞术分析适应性和先天性免疫细胞群体。建立脂多糖（LPS）诱导的骨髓来源巨噬细胞（BMDM）。采用qRT-PCR和免疫印迹分析确定炎症相关生物标志物的水平。采用ELISA法测定包括IL-1β、IL-6和TNF在内的炎性细胞因子的释放。
结果
巨噬细胞中DCAF1缺乏并未影响骨髓和脾脏中的免疫细胞群体。DCAF1抑制LPS诱导的BMDM中的炎性细胞因子。此外，巨噬细胞中DCAF1缺乏导致严重症状，包括股骨细菌载量减少、皮质骨丢失和反应性骨形成。机制研究表明，DCAF1缺乏诱导p38过度激活。
讨论
巨噬细胞中的DCAF1抑制脂多糖诱导的小鼠骨髓炎模型。
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