F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and...

Area of Science:

• Immunology
• Molecular Biology
• Pathology

Background:

• Osteomyelitis is a bone infection involving macrophages and inflammation.
• F-Box and WD repeat domain containing 7 (Fbxw7) is a tumor suppressor and E3 ubiquitin ligase.
• The role of Fbxw7 in osteomyelitis pathogenesis is not well understood.

Purpose of the Study:

• To investigate the role of Fbxw7 in osteomyelitis.
• To explore the molecular mechanisms by which Fbxw7 influences osteomyelitis progression.

Main Methods:

• Measured Fbxw7 mRNA levels in patient bone marrow cells and S. aureus-infected macrophages.
• Generated Fbxw7 conditional knockout mice lacking Fbxw7 in myeloid cells.
• Assessed inflammatory cytokine expression (IL-6, IL-23a, Nos2) in Fbxw7-deficient macrophages.
• Evaluated osteomyelitis severity (weight loss, bacterial burden, bone loss) in knockout mice.
• Identified Fbxw7 interacting partners and tested their interaction.

Main Results:

• Fbxw7 expression was elevated in osteomyelitis patients and S. aureus-infected macrophages.
• Fbxw7 deficiency suppressed IL-6, IL-23a, and Nos2 expression in infected macrophages.
• Fbxw7 knockout mice exhibited reduced weight loss, lower bacterial burden, and less bone loss.
• Fbxw7 interacted with MYB, and its deficiency led to increased MYB levels and reduced MYB ubiquitination.

Conclusions:

• Fbxw7 promotes osteomyelitis symptoms.
• Fbxw7 regulates osteomyelitis by controlling MYB ubiquitination and stability.