Ddb1-Cullin4-Associated-Factor 1 in Macrophages Restricts the Staphylococcus aureus-Induced Osteomyelitis
Yang Zong,1,* Haojie Shan,1,* Fuli Yin,1 Xin Ma,1 Chaolai Jiang,1 Nan Wang,2 Lihui Zhou,3 Yiwei Lin,1 Zubin Zhou,1 Xiaowei Yu1 1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 2Depa...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/a356e0c07cc5442b9f6d7f59c97600f0 |
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| Sumario: | Yang Zong,1,* Haojie Shan,1,* Fuli Yin,1 Xin Ma,1 Chaolai Jiang,1 Nan Wang,2 Lihui Zhou,3 Yiwei Lin,1 Zubin Zhou,1 Xiaowei Yu1 1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 3Department of Orthopaedic Surgery, Xiangshan First People’s Hospital, Ningbo, Zhejiang, 315700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaowei YuDepartment of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of ChinaTel + 86-21-3829-7774Email yuxw@sjtu.edu.cnIntroduction: 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: Staphylococcus aureus-induced mouse model of osteomyelitis was established on the DCAF1fl/flLyz2cre/+ and DCAF1fl/flLyz2+/+ (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 Staphylococcus aureus-induced mouse model of osteomyelitis.Keywords: DCAF1, macrophages, Staphylococcus aureus, osteomyelitis, inflammation |
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