PMID- 33953594 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220422 IS - 1178-7031 (Print) IS - 1178-7031 (Electronic) IS - 1178-7031 (Linking) VI - 14 DP - 2021 TI - Ddb1-Cullin4-Associated-Factor 1 in Macrophages Restricts the Staphylococcus aureus-Induced Osteomyelitis. PG - 1667-1676 LID - 10.2147/JIR.S307316 [doi] AB - 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: Staphylococcus aureus-induced mouse model of osteomyelitis was established on the DCAF1(fl/fl)Lyz2(cre/+) and DCAF1(fl/fl)Lyz2(+/+) (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-1beta, 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. CI - (c) 2021 Zong et al. FAU - Zong, Yang AU - Zong Y AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Shan, Haojie AU - Shan H AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Yin, Fuli AU - Yin F AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Ma, Xin AU - Ma X AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Jiang, Chaolai AU - Jiang C AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Wang, Nan AU - Wang N AD - Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China. FAU - Zhou, Lihui AU - Zhou L AD - Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo, Zhejiang, 315700, People's Republic of China. FAU - Lin, Yiwei AU - Lin Y AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Zhou, Zubin AU - Zhou Z AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. FAU - Yu, Xiaowei AU - Yu X AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China. LA - eng PT - Journal Article DEP - 20210428 PL - New Zealand TA - J Inflamm Res JT - Journal of inflammation research JID - 101512684 PMC - PMC8091595 OTO - NOTNLM OT - DCAF1 OT - Staphylococcus aureus OT - inflammation OT - macrophages OT - osteomyelitis COIS- The authors report no conflicts of interest in this work. EDAT- 2021/05/07 06:00 MHDA- 2021/05/07 06:01 PMCR- 2021/04/28 CRDT- 2021/05/06 07:00 PHST- 2021/02/18 00:00 [received] PHST- 2021/04/12 00:00 [accepted] PHST- 2021/05/06 07:00 [entrez] PHST- 2021/05/07 06:00 [pubmed] PHST- 2021/05/07 06:01 [medline] PHST- 2021/04/28 00:00 [pmc-release] AID - 307316 [pii] AID - 10.2147/JIR.S307316 [doi] PST - epublish SO - J Inflamm Res. 2021 Apr 28;14:1667-1676. doi: 10.2147/JIR.S307316. eCollection 2021.