SMU-KI International Immunopharmacology Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Front Immunol. 2022 Feb 15;13:833040. doi: 10.3389/fimmu.2022.833040. eCollection 2022.
Bone loss due to an increased osteoclast activity is common in osteoporosis and rheumatoid arthritis. For the first time, we observed an inhibition of osteoclast formation and bone resorption by outer-membrane vesicles (OMVs) from a Gram-negative, pathogenic bacterium, (P.M). Gene ontogeny and KEGG enrichment analyses of miRNA and mRNA sequencing data demonstrated a significant effect of P.M OMVs on mitochondrial functions and apoptotic pathways. OMVs induced mitochondrial dysfunction through an increased level of intracellular ROS, collapse of mitochondrial membrane potential (ΔΨm), and modulation of Bax, Bcl-2, caspase-3, and cytochrome c expression. In addition, P.M OMVs strongly inhibited miR-96-5p expression, which caused an upregulation of ATP binding cassette subfamily A member 1 (Abca1) in osteoclasts leading to an increased level of mitochondria-dependent apoptosis. Moreover, treatment with P.M but not OMVs attenuated bone loss in experimental osteoporosis and collagen-induced arthritis. Collectively, we demonstrated osteoprotective functions of OMVs from , which downregulated miR-96-5p causing an increased Abca1 expression and mitochondria-dependent apoptosis.
由于破骨细胞活性增加导致的骨质流失在骨质疏松症和类风湿性关节炎中很常见。我们首次观察到革兰氏阴性、致病性细菌（P.M）的外膜囊泡（OMV）抑制破骨细胞形成和骨吸收。miRNA 和 mRNA 测序数据的基因发生分析和 KEGG 富集分析表明，P.M OMVs 对线粒体功能和凋亡途径有显著影响。OMVs 通过增加细胞内 ROS 水平、线粒体膜电位（ΔΨm）崩溃以及 Bax、Bcl-2、caspase-3 和细胞色素 c 表达的调节来诱导线粒体功能障碍。此外，P.M OMVs 强烈抑制 miR-96-5p 的表达，导致破骨细胞中 ATP 结合盒亚家族 A 成员 1（Abca1）的上调，从而导致依赖线粒体的凋亡增加。此外，用 P.M 而不是 OMVs 处理可减轻实验性骨质疏松症和胶原诱导性关节炎中的骨质流失。总的来说，我们证明了 的 OMVs 具有骨保护功能，它下调了 miR-96-5p，导致 Abca1 表达增加和依赖线粒体的凋亡。
