PMID- 34378805 OWN - NLM STAT- MEDLINE DCOM- 20220504 LR - 20220504 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 237 IP - 1 DP - 2022 Jan TI - Merlin functions as a critical regulator in Staphylococcus aureus-induced osteomyelitis. PG - 815-823 LID - 10.1002/jcp.30550 [doi] AB - 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/fl) Lyz2(cre/+) and Merlin(fl/fl) Lyz2(+/+) 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/fl) Lyz2(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. CI - (c) 2021 Wiley Periodicals LLC. FAU - Zhou, Zubin AU - Zhou Z AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Chen, Yuanliang AU - Chen Y AD - Department of Orthopaedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, Haikou, Hainan, China. FAU - Min, Hong Sung AU - Min HS AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Wan, Yongbai AU - Wan Y AD - Department of Orthopaedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, Haikou, Hainan, China. FAU - Shan, Haojie AU - Shan H AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Lin, Yiwei AU - Lin Y AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Xia, Wenyang AU - Xia W AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Yin, Fuli AU - Yin F AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Jiang, Chaolai AU - Jiang C AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Yu, Xiaowei AU - Yu X AUID- ORCID: 0000-0002-8235-4907 AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210811 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Neurofibromin 2) SB - IM MH - Animals MH - Cytokines MH - Humans MH - Lipopolysaccharides/pharmacology MH - Mice MH - Neurofibromin 2/genetics/metabolism MH - *Osteomyelitis MH - *Staphylococcal Infections MH - Staphylococcus aureus/metabolism OTO - NOTNLM OT - DCAF1 OT - Merlin OT - Staphylococcus aureus OT - inflammatory response OT - osteomyelitis EDAT- 2021/08/12 06:00 MHDA- 2022/05/06 06:00 CRDT- 2021/08/11 09:08 PHST- 2021/07/12 00:00 [revised] PHST- 2021/04/19 00:00 [received] PHST- 2021/08/02 00:00 [accepted] PHST- 2021/08/12 06:00 [pubmed] PHST- 2022/05/06 06:00 [medline] PHST- 2021/08/11 09:08 [entrez] AID - 10.1002/jcp.30550 [doi] PST - ppublish SO - J Cell Physiol. 2022 Jan;237(1):815-823. doi: 10.1002/jcp.30550. Epub 2021 Aug 11.