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

IF 5.5 2区 医学 Q2 MICROBIOLOGY
Journal of Oral Microbiology Pub Date : 2025-08-08 eCollection Date: 2025-01-01 DOI:10.1080/20002297.2025.2540823
Yongyong Yan, Haiyan Wang, Huizhi Deng, Haokun He, Qing Ge, Jun Zha, Jun Chen, Qing Zhang, Haiyan Deng, Gang Wu, Richard T Jaspers, Janak L Pathak
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引用次数: 0

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.

牙龈卟啉单胞菌omv通过SAA3/TLR4/MyD88/NF-κB轴抑制BMSCs成骨分化。
背景:牙周炎引起的牙槽骨丢失是牙齿丢失的主要原因。牙龈卟啉单胞菌(P. gingivalis)是牙周炎的主要致病菌。来源于牙龈假单胞菌(p.g - omv)的外膜囊泡(omv)含有多种生物活性分子,一些研究表明,p.g - omv可能参与牙周炎引起的牙槽骨丢失。材料和方法:分离并表征了p - g- omv。分析pg - omvs对骨髓间充质干细胞增殖和成骨分化的影响。对骨髓间充质干细胞进行了高通量测序、RT-qPCR和Western blot分析,以揭示潜在的分子机制。结果:pg - omvs促进骨髓间充质干细胞增殖,抑制其成骨分化。高通量测序结果显示,血清淀粉样蛋白A (SAA),尤其是SAA3,在p.g - omv处理的骨髓间充质干细胞中显著上调。SAA3上调可促进TLR4、MyD88和NF-κB p65,抑制p - g- omv处理的骨髓间充质干细胞成骨分化。在骨髓间充质干细胞中,SAA3的表达下调了p.g - omvs诱导的TLR4、MyD88和NF-κB p65,并恢复了p.g - omvs抑制的成骨分化。结论:我们的研究结果表明,p.g - omv通过saa3介导的TLR4/MyD88/NF-κB轴抑制BMSCs的成骨分化,为治疗牙周炎诱导的牙槽骨丢失提供了新的靶点。
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来源期刊
CiteScore
8.00
自引率
4.40%
发文量
52
审稿时长
12 weeks
期刊介绍: As the first Open Access journal in its field, the Journal of Oral Microbiology aims to be an influential source of knowledge on the aetiological agents behind oral infectious diseases. The journal is an international forum for original research on all aspects of ''oral health''. Articles which seek to understand ''oral health'' through exploration of the pathogenesis, virulence, host-parasite interactions, and immunology of oral infections are of particular interest. However, the journal also welcomes work that addresses the global agenda of oral infectious diseases and articles that present new strategies for treatment and prevention or improvements to existing strategies. Topics: ''oral health'', microbiome, genomics, host-pathogen interactions, oral infections, aetiologic agents, pathogenesis, molecular microbiology systemic diseases, ecology/environmental microbiology, treatment, diagnostics, epidemiology, basic oral microbiology, and taxonomy/systematics. Article types: original articles, notes, review articles, mini-reviews and commentaries
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