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

Backgrounds: Periodontitis-induced alveolar bone loss is a primary cause of tooth loss. () is the primary pathogenic bacterium of periodontitis. Outer membrane vesicles (OMVs) derived from (-OMVs) contain various bioactive molecules, and several studies have suggested that -OMVs may participate in alveolar bone loss caused by periodontitis.

Materials And Methods: -OMVs were isolated and characterized. The effect of -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: -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 -OMVs-treated BMSCs. Upregulated SAA3 promoted TLR4, MyD88, and NF-κB p65 and inhibited osteogenic differentiation of -OMVs-treated BMSCs. The knockdown of SAA3 in BMSCs downregulated -OMVs-induced TLR4, MyD88, and NF-κB p65 and rescued -OMVs-inhibited osteogenic differentiation.

Conclusions: Our results indicate that -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.