Benzylurea Protects hPDLFs Against LPS-Induced Mitochondrial Dysfunction Through MTCH2

Area of Science:

• Cell Biology
• Biochemistry
• Periodontal Medicine

Background:

• Periodontal ligament fibroblasts (hPDLFs) are crucial for maintaining tooth health.
• Inflammatory injuries can compromise hPDLF function and contribute to periodontal disease.
• Understanding protective mechanisms against such injuries is vital for therapeutic development.

Purpose of the Study:

• To elucidate the mechanism by which benzylurea mitigates inflammatory injury in hPDLFs.
• To investigate benzylurea's effects on cellular pathways, including nuclear factor-kappa B (NF-κB) signaling and mitochondrial function.
• To explore the roles of mitochondrial carrier homolog 2 (MTCH2) and Cytochrome b5 type B (CYB5B) in benzylurea's protective effects.

Main Methods:

• Established an LPS-induced inflammation model in hPDLFs.
• Assessed NF-κB nuclear translocation, inflammatory cytokine secretion, and F-actin organization.
• Evaluated mitochondrial function via mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) opening, and reactive oxygen species (ROS) levels.
• Quantified the expression of MTCH2 and CYB5B.

Main Results:

• Benzylurea mitigated LPS-induced hPDLF proliferation inhibition and apoptosis.
• Benzylurea reduced inflammatory cytokine release and NF-κB nuclear translocation.
• Benzylurea enhanced mitochondrial function by stabilizing MMP and preventing mPTP opening.
• LPS increased MTCH2 and decreased CYB5B expression; benzylurea reversed these changes.
• MTCH2 expression directly influenced CYB5B levels, cytokine release, and NF-κB activation.

Conclusions:

• CYB5B may function as an effector protein regulated by MTCH2.
• Benzylurea enhances mitochondrial function and protects hPDLFs from LPS-induced damage.
• The protective mechanism involves the MTCH2-CYB5B pathway, highlighting benzylurea's therapeutic potential in periodontal inflammation.