Post-doc Nova Southeastern University Davie, Florida, United States
Disclosure(s):
Satoru Shindo, DDS, PhD: No financial relationships to disclose
Introduction/Rationale: Phosphoglycerol dihydroceramides (PGDHCs) produced by Porphyromonas gingivalis (Pg) are emerging virulence factors that contribute to periodontal inflammation and alveolar bone destruction. Macrophage mechanosensing mediated by Piezo1 plays a crucial role in regulating inflammatory signaling and osteoclastogenesis. However, whether bacterial lipid metabolites interfere with Piezo1-dependent mechanotransduction in macrophages remains unknown. This study examined the impact of Pg–derived PGDHC on macrophage mechanosensing and its contribution to periodontal bone loss.
Methods: Bone marrow–derived macrophages (BMDMs) were stimulated with wild-type Pg (Pg WT), a serine palmitoyltransferase–deficient strain lacking PGDHC (Pg SPT-null), or purified PGDHC. Piezo1 activity was assessed by Yoda1-induced Ca²⁺ influx. Osteoclastogenesis from BMDMs was evaluated following Piezo1 activation in the presence or absence of PGDHC. The role of non-muscle myosin IIA (MYH9) was examined using immunofluorescence, blebbistatin, and siRNA-mediated Myh9 silencing. Experimental periodontitis was induced by ligature placement with oral inoculation of Pg WT or Pg SPT-null for 14 days, and alveolar bone loss was quantified by micro-CT.
Results: Pg WT and purified PGDHC significantly suppressed Piezo1-mediated Ca²⁺ influx in macrophages, whereas Pg SPT-null and other oral bacteria had no effect. PGDHC counteracted Piezo1 activation–mediated suppression of osteoclast differentiation. PGDHC colocalized with MYH9, and both blebbistatin treatment and Myh9 silencing disrupted Piezo1-mediated Ca²⁺ influx. In vivo, Pg WT inoculation induced significantly greater periodontal bone loss than Pg SPT-null.
Conclusion: Pg-derived PGDHC impairs Piezo1-mediated mechanosensing in macrophages through MYH9-dependent cytoskeletal regulation, thereby promoting osteoclastogenesis and periodontal bone loss, and identifying PGDHC inhibition as a potential therapeutic strategy for periodontitis.
