Porphyromonas gingivalis Vesicles Control Osteoclast-Macrophage Lineage Fate

Area of Science:

• Oral microbiology
• Immunology
• Cell biology

Background:

• Porphyromonas gingivalis (Pg) is a key pathogen in chronic periodontitis.
• Pg releases outer membrane vesicles (OMVs) that spread virulence factors.
• The effect of Pg-OMVs on monocyte-macrophage/osteoclast differentiation is not well understood.

Purpose of the Study:

• To investigate the impact of Pg-OMVs on osteoclast (OC) and macrophage (MΦ) differentiation from RAW264.7 cells.
• To determine if the timing of Pg-OMV exposure influences differentiation outcomes.
• To explore the role of OC-STAMP in Pg-OMV-mediated effects.

Main Methods:

• Isolated OMVs from Pg W83.
• Treated RAW264.7 cells with OMVs and RANKL using three different schedules.
• Assessed osteoclastogenesis, M1 macrophage polarization, and expression of key markers (dc-stamp, oc-stamp, nfatc1, acp5).
• Utilized a monoclonal antibody against OC-STAMP to block its function.

Main Results:

• Simultaneous Pg-OMV and RANKL exposure suppressed osteoclastogenesis and promoted M1 polarization.
• Delayed Pg-OMV exposure enhanced osteoclastogenesis and reduced M1 polarization.
• OC-STAMP antibody partially reversed the enhanced osteoclastogenesis in delayed exposure groups.
• Pg-OMV phagocytosis levels inversely correlated with osteoclast formation.

Conclusions:

• Pg-OMVs exhibit stage-specific effects on OC/MΦ lineage differentiation.
• Early Pg-OMV exposure inhibits osteoclast formation and favors M1 macrophages.
• Later Pg-OMV exposure promotes osteoclast formation without M1 polarization.
• Pg-OMVs may significantly influence periodontal lesion progression and tissue damage.