PMID- 36858599 OWN - NLM STAT- MEDLINE DCOM- 20230526 LR - 20230526 IS - 1884-2836 (Electronic) IS - 1344-6304 (Linking) VI - 76 IP - 3 DP - 2023 May 24 TI - Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2 Ubiquitination. PG - 197-203 LID - 10.7883/yoken.JJID.2022.515 [doi] AB - Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP(-/-)) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP(-/-) mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-kappaB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-kappaB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP(-/-) mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination. FAU - Chen, Yuanliang AU - Chen Y AD - Department of Orthopedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, China. FAU - Wan, Yongbai AU - Wan Y AD - Department of Orthopedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, China. FAU - Shan, Haojie AU - Shan H AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. FAU - Lin, Yiwei AU - Lin Y AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. FAU - Xia, Wenyang AU - Xia W AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. FAU - Yin, Fuli AU - Yin F AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. FAU - Jiang, Chaolai AU - Jiang C AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. FAU - Shi, Zhongmin AU - Shi Z AD - Department of Orthopedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. LA - eng PT - Journal Article DEP - 20230228 PL - Japan TA - Jpn J Infect Dis JT - Japanese journal of infectious diseases JID - 100893704 RN - 0 (NF-kappa B) RN - 0 (Lipopolysaccharides) RN - EC 3.4.19.12 (Ubiquitin-Specific Proteases) RN - EC 2.7.11.1 (Ripk2 protein, mouse) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2) SB - IM MH - Mice MH - Animals MH - NF-kappa B MH - Lipopolysaccharides/pharmacology MH - Staphylococcus aureus MH - Ubiquitination MH - *Osteomyelitis MH - *Communicable Diseases MH - Ubiquitin-Specific Proteases/genetics MH - Receptor-Interacting Protein Serine-Threonine Kinase 2 OTO - NOTNLM OT - NF-kappaB OT - RIPK2 OT - USP8 OT - osteomyelitis OT - ubiquitination EDAT- 2023/03/02 06:00 MHDA- 2023/05/26 06:42 CRDT- 2023/03/01 20:54 PHST- 2023/05/26 06:42 [medline] PHST- 2023/03/02 06:00 [pubmed] PHST- 2023/03/01 20:54 [entrez] AID - 10.7883/yoken.JJID.2022.515 [doi] PST - ppublish SO - Jpn J Infect Dis. 2023 May 24;76(3):197-203. doi: 10.7883/yoken.JJID.2022.515. Epub 2023 Feb 28.