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Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling
Molecular Oral Microbiology ( IF 2.8 ) Pub Date : 2020-07-23 , DOI: 10.1111/omi.12307
Min‐Kyoung Song 1 , Hyun Young Kim 2 , Bong‐Kyu Choi 2 , Hong‐Hee Kim 1
Affiliation  

Filifactor alocis, an asaccharolytic anaerobic Gram‐positive rod (AAGPR), is an emerging marker of periodontitis. Severe periodontitis causes destruction of the alveolar bone that supports teeth and can even lead to tooth loss. Based on our previous report that F. alocis‐derived extracellular vesicles (FA EVs) contain various effector molecules and have immunostimulatory activity, we investigated the effect of FA EVs on osteogenesis using mouse bone‐derived mesenchymal stromal cells (BMSCs). FA EVs dramatically inhibited bone mineralization similar to whole bacteria and reduced the expression levels of osteogenic marker genes. The osteogenic differentiation of TLR2‐deficient BMSCs was not inhibited by FA EVs, suggesting that their inhibitory effect on osteogenesis is dependent on TLR2 signaling. FA EVs effectively activated TLR2 downstream signaling of the MAPK and NF‐κB pathways. In addition, FA EVs regulated RANKL and OPG gene expression, increasing the RANKL/OPG ratio in BMSCs in a TLR2‐dependent manner. Our study suggests that F. alocis‐derived EVs interfere with bone metabolism via TLR2 activation, providing insight into the pathogenesis of bone loss associated with periodontitis.

中文翻译:

丝状海芋来源的细胞外囊泡通过TLR2信号传导抑制成骨

丝状无刺革兰厌氧菌革兰氏阳性棒(AAGPR)是牙周炎的新兴标志。严重的牙周炎会破坏支持牙齿的牙槽骨,甚至会导致牙齿脱落。根据我们之前的报告,海芋衍生的细胞外囊泡(FA EVs)包含各种效应分子并具有免疫刺激活性,我们使用小鼠骨骼衍生的间充质基质细胞(BMSCs)研究了FA EVs对成骨的影响。FA EV可以像整个细菌一样显着抑制骨矿化并降低成骨标记基因的表达水平。FA EV不能抑制TLR2缺陷型BMSC的成骨分化,这表明它们对成骨的抑制作用取决于TLR2信号传导。FA EV可以有效激活MAPK和NF-κB途径的TLR2下游信号传导。另外,FA EV调节RANKL和OPG基因表达,以TLR2依赖性方式增加BMSC中RANKL / OPG的比率。我们的研究表明,海芋衍生的电动车通过TLR2激活干扰骨代谢,从而深入了解与牙周炎有关的骨质流失的发病机理。
更新日期:2020-09-26
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