Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea.
Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.
Mol Oral Microbiol. 2020 Oct;35(5):202-210. doi: 10.1111/omi.12307. Epub 2020 Aug 14.
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.
栖牙密螺旋体，一种无碳源厌氧革兰阳性杆菌（AAGPR），是牙周炎的一个新兴标志物。严重的牙周炎会导致支撑牙齿的牙槽骨破坏，甚至导致牙齿脱落。基于我们之前的报告，栖牙密螺旋体来源的细胞外囊泡（FA EVs）含有各种效应分子，具有免疫刺激活性，我们使用鼠源性骨髓间充质基质细胞（BMSCs）研究了 FA EVs 对成骨的影响。FA EVs 可显著抑制类似于全细菌的骨矿化，并降低成骨标记基因的表达水平。FA EVs 对 TLR2 缺陷型 BMSCs 的成骨分化没有抑制作用，表明其对成骨的抑制作用依赖于 TLR2 信号通路。FA EVs 可有效激活 TLR2 下游的 MAPK 和 NF-κB 通路信号。此外，FA EVs 调节 RANKL 和 OPG 基因表达，以 TLR2 依赖的方式增加 BMSCs 中的 RANKL/OPG 比值。我们的研究表明，栖牙密螺旋体来源的 EVs 通过 TLR2 激活干扰骨代谢，为牙周炎相关骨丢失的发病机制提供了新的见解。
