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Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2

Yuanliang Chen1, Yongbai Wan1, Haojie Shan2

  • 1Department of Orthopedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, China.

Japanese Journal of Infectious Diseases
|March 1, 2023
PubMed

Insights

Ubiquitin-specific peptidase 8 (USP8) is crucial for inflammation in osteomyelitis by regulating Receptor-interacting serine/threonine kinase 2 (RIPK2) ubiquitination. USP8 deficiency ameliorates Staphylococcus aureus-induced osteomyelitis symptoms in mice.

Area of Science:

  • Immunology
  • Molecular Biology
  • Bone Biology

Background:

  • Receptor-interacting serine/threonine kinases (RIPKs) play roles in inflammation and immune responses.
  • Osteomyelitis, a bone infection, involves complex inflammatory pathways.

Purpose of the Study:

  • To investigate the role of RIPK2 in osteomyelitis.
  • To identify upstream regulators of RIPK2, focusing on ubiquitin-specific peptidase 8 (USP8).

Main Methods:

  • Established a Staphylococcus aureus-induced osteomyelitis mouse model using wild-type and USP8-deficient mice.
  • Isolated bone marrow-derived macrophages (BMDMs) for in vitro analysis.
  • Utilized Enzyme-linked immunosorbent assays, quantitative PCR, and immunoblot analysis to assess inflammatory markers.

Main Results:

  • USP8 promotes RIPK2-mediated NF-κB activation and inflammatory cytokine production in BMDMs stimulated with LPS, CpG, or PAM3CSK4.
  • USP8 deficiency led to ameliorated osteomyelitis symptoms in mice, including reduced bone loss and bacterial load.
  • USP8 critically targets RIPK2 ubiquitination in the context of Staphylococcus aureus-induced osteomyelitis.

Conclusions:

  • USP8 is essential for RIPK2-mediated inflammatory signaling in osteomyelitis.
  • USP8 deficiency confers protection against Staphylococcus aureus-induced osteomyelitis.
  • Targeting USP8 may offer a therapeutic strategy for osteomyelitis.
Keywords:
NF-κBRIPK2USP8osteomyelitisubiquitination

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