Work

Porphyromonas gingivalis OMVs inhibit osteogenic differentiation of BMSCs via SAA3/TLR4/MyD88/NF-κB axis

Year: 2025

Type: article

Abstract: Backgrounds Periodontitis-induced alveolar bone loss is a primary cause of tooth loss. Porphyromonas gingivalis (P. gingivalis) is the primary pathogenic bacterium of periodontitis. Outer membrane vesicles (OMVs) derived from P. gingivalis (P.g-OMVs) contain various bioactive molecules, and several studies have suggested that P.g-OMVs may participate in alveolar bone loss caused by periodontitis.Materials and Methods P.g-OMVs were isolated and characterized. The effect of P.g-OMVs on BMSCs proliferation and osteogenic differentiation was analyzed. High-throughput sequencing, RT-qPCR, and Western blot analysis were performed in BMSCs to unravel the underlying molecular mechanism.Results P.g-OMVs promoted proliferation but inhibited osteogenic differentiation of BMSCs. High-throughput sequencing results showed that serum amyloid A (SAA), especially SAA3, was robustly upregulated in P.g-OMVs-treated BMSCs. Upregulated SAA3 promoted TLR4, MyD88, and NF-κB p65 and inhibited osteogenic differentiation of P.g-OMVs-treated BMSCs. The knockdown of SAA3 in BMSCs downregulated P.g-OMVs-induced TLR4, MyD88, and NF-κB p65 and rescued P.g-OMVs-inhibited osteogenic differentiation.Conclusions Our results indicate that P.g-OMVs inhibit osteogenic differentiation of BMSCs via the SAA3-mediated TLR4/MyD88/NF-κB axis, providing novel targets for the treatment of periodontitis-induced alveolar bone loss.

Source: Journal of Oral Microbiology

DOI: 10.1080/20002297.2025.2540823