Apoptotic extracellular vesicles alleviate Pg‐LPS induced inflammatory responses of macrophages via AMPK/SIRT1/NF‐κB pathway and inhibit osteoclast formation

作者：Qingyuan Ye, Haokun Xu, Shiyu Liu, Zihan Li, Jun Zhou, Feng Ding, Xige Zhang, Yazheng Wang, Yan Jin, Qintao Wang · 发表于：Journal of Periodontology · 年份：2022 · DOI：10.1002/jper.21-0657 · 被引用次数：79 · 研究领域：Oral microbiology and periodontitis research、Extracellular vesicles in disease、Biomarkers in Disease Mechanisms

BACKGROUND: Periodontitis is caused by the imbalance of anti-bacteria immune response and excessive inflammation whereas macrophages play an important role in inflammation. Thus, it is critical for finding efficient anti-inflammatory strategies to alleviate periodontal inflammation and prevent bone destruction. Apoptosis of mesenchymal stem cells (MSCs) exerts immune silencing effects, however, using these effects to develop anti-inflammatory strategies remains unknown. In our study, we extracted apoptotic extracellular vesicles (ApoEVs) from bone marrow MSCs (BMMSCs) and found ApoEVs inhibited macrophages polarizing into proinflammatory condition via AMPK/SIRT1/NF-κB pathway. Besides that, we also found ApoEVs inhibited adjacent osteoclast formation by suppressing the secretion of TNF-α of proinflammatory macrophages. METHODS: BMMSCs derived ApoEVs were extracted by gradient centrifugation. Protein expression level and secreted cytokines of ApoEVs treated macrophages were examined by western blot and ELISA, respectively. Besides, the change of NF-κB pathway and related molecules were examined by immunofluorescence and western blot. The osteoclast formation under the different conditioned mediums from macrophages was measured by TRAP staining, MMP-9 expression, and pit assay. RESULTS: ApoEVs were extracted from staurosporine-induced apoptotic BMMSCs and were in sphere shapes whose diameters are between 100 and 1000 nm. ApoEVs could be phagocyted by macrophages and in turn red...