Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss.
Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss.
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TNF-α处理的人牙龈源性MSCs外泌体增强M2巨噬细胞极化，抑制牙周骨质流失。
DOI：
10.1016/j.actbio.2020.12.046
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发表时间：
2021-03-01
影响因子：
9.7
通讯作者：
Nishimura F
中科院分区：
文献类型：
--
作者：
Nakao Y;Fukuda T;Zhang Q;Sanui T;Shinjo T;Kou X;Chen C;Liu D;Watanabe Y;Hayashi C;Yamato H;Yotsumoto K;Tanaka U;Taketomi T;Uchiumi T;Le AD;Shi S;Nishimura F
间充质干细胞（MSC）衍生的外泌体在涉及MSC的无细胞治疗中起着核心作用，并且可以根据疾病相关的微环境定制内容物。然而，最佳的MSC预处理，以提高其治疗潜力在很大程度上是未知的。在这里，我们表明，牙龈组织来源的骨髓间充质干细胞（GMSCs）与肿瘤坏死因子-α（TNF-α）的预处理是理想的牙周炎的治疗。TNF-α刺激不仅增加了GMSC分泌的外泌体的量，而且还增强了CD 73的外泌体表达，从而诱导抗炎的M2巨噬细胞极化。通过小鼠结扎性牙周炎模型检测GMSC来源的exosomes对炎性骨丢失的影响。局部注射GMSC来源的外泌体可显着减少牙周骨吸收和抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞的数量，并且这些作用通过用TNF-α预处理GMSC进一步增强。因此，GMSC衍生的外泌体也表现出抗破骨细胞生成活性。在牙周膜细胞（PDLCs）中，Wnt 5 a可调控NF-κB配体受体激活因子（RANKL）的表达，而外泌体miR-1260 B b可靶向Wnt 5 a介导的RANKL通路并抑制其破骨细胞生成活性。这些结果表明，TNF-α预处理的GMSC衍生的外泌体调节炎症和破骨细胞生成的显著能力为建立牙周炎的治疗方法铺平了道路。
Mesenchymal stem cell (MSC)–derived exosome plays a central role in the cell-free therapeutics involving MSCs and the contents can be customized under disease-associated microenvironments. However, optimal MSC-preconditioning to enhance its therapeutic potential is largely unknown. Here, we show that preconditioning of gingival tissue-derived MSCs (GMSCs) with tumor necrosis factor-alpha (TNF-α) is ideal for the treatment of periodontitis. TNF-α stimulation not only increased the amount of exosome secreted from GMSCs, but also enhanced the exosomal expression of CD73, thereby inducing anti-inflammatory M2 macrophage polarization. The effect of GMSC-derived exosomes on inflammatory bone loss were examined by ligature-induced periodontitis model in mice. Local injection of GMSC-derived exosomes significantly reduced periodontal bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and these effects were further enhanced by preconditioning of GMSCs with TNF-α. Thus, GMSC-derived exosomes also exhibited anti-osteoclastogenic activity. Receptor activator of NF-κB ligand (RANKL) expression was regulated by Wnt5a in periodontal ligament cells (PDLCs), and exosomal miR-1260b was found to target Wnt5a-mediated RANKL pathway and inhibit its osteoclastogenic activity. These results indicate that significant ability of the TNF-α-preconditioned GMSC-derived exosomes to regulate inflammation and osteoclastogenesis paves the way for establishment of a therapeutic approach for periodontitis.
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影响因子：
4.3
作者：
Carnes, DL;Maeder, CL;Graves, DT
通讯作者：
Graves, DT
影响因子：
4.4
作者：
Clayton, Aled;Al-Taei, Saly;Tabi, Zsuzsanna
通讯作者：
Tabi, Zsuzsanna
影响因子：
4
作者：
David, JP;Sabapathy, K;Wagner, EF
通讯作者：
Wagner, EF
影响因子：
--
作者：
Feng F;Jiang Y;Lu H;Lu X;Wang S;Wang L;Wei M;Lu W;Du Z;Ye Z;Yang G;Yuan F;Ma Y;Lei X;Lu Z
通讯作者：
Lu Z
影响因子：
2.2
作者：
Abe, Toshiharu;Hajishengallis, George
通讯作者：
Hajishengallis, George