Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis.
Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis.
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来自缺氧预条件牙髓干细胞的小细胞外囊泡通过调节巨噬细胞极化和破骨细胞生成来改善炎症性骨溶解。
DOI：
10.1016/j.bioactmat.2022.10.001
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发表时间：
2023-04
影响因子：
18.9
通讯作者：
Wei, Xi
中科院分区：
文献类型：
--
作者：
Tian, Jun;Chen, Weiyang;Xiong, Yuhua;Li, Qianer;Kong, Siyi;Li, Mengjie;Pang, Chunfeng;Qiu, Yu;Xu, Zhezhen;Gong, Qimei;Wei, Xi
广泛的巨噬细胞炎症反应和破骨细胞形成是主要的炎症或感染性骨质溶解。间充质干细胞（MSC）衍生的小细胞外囊泡（MSC-sEV）已被证明对骨缺损发挥治疗作用。然而，培养的MSC通常在体外暴露于常氧（21%O2），这与缺氧条件下体内的氧浓度有很大不同。目前尚不清楚在低氧条件下培养的牙髓干细胞（DPSC）的sEV（Hypo-sEV）是否比在常氧条件下培养的sEV（Nor-sEV）对脂多糖（LPS）诱导的炎性骨质溶解具有更好的治疗效果，因为它们同时抑制巨噬细胞炎症反应和破骨细胞生成。在这项研究中，我们表明，缺氧显着诱导从DPSC的sEV的释放。此外，与Nor-sEV相比，Hypo-sEV在促进M2巨噬细胞极化和抑制破骨细胞形成以减轻LPS诱导的炎症性颅骨骨丢失方面表现出显著改善的功效。从机制上讲，缺氧预处理显著改变了DPSC-sEV的miRNA谱。MiR-210- 3 p富含Hypo-sEV，可同时诱导M2巨噬细胞生成并通过靶向NF-κB1 p105抑制破骨细胞生成，从而减弱骨质溶解。我们的研究表明，缺氧诱导的DPSC-sEV治疗炎症性或感染性骨质溶解的潜力很大，并确定了miR-210- 3 p通过抑制NF-κ B1表达同时阻碍破骨细胞生成和巨噬细胞炎症反应的新作用。缺氧促进DPSC释放sEV。缺氧诱导的DPSC-sEV（Hypo-sEV）显示出增加的抑制炎性骨溶解的潜力。在Hypo-sEV中富集的miR-210- 3 p有助于Hypo-sEV的治疗作用。miR-210- 3 p通过靶向NF-κB1同时诱导M2巨噬细胞生成并抑制破骨细胞生成。缺氧诱导的DPSC-sEV代表了一种有希望的治疗炎症性骨质溶解的方法。
Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) have been shown to exert therapeutic effects on bone defects. However, cultured MSCs are typically exposed to normoxia (21% O2) in vitro, which differs largely from the oxygen concentration in vivo under hypoxic conditions. It is largely unknown whether sEV derived from dental pulp stem cells (DPSCs) cultured under hypoxic conditions (Hypo-sEV) exert better therapeutic effects on lipopolysaccharide (LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions (Nor-sEV) by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis. In this study, we show that hypoxia significantly induces the release of sEV from DPSCs. Moreover, Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV. Mechanistically, hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV. MiR-210-3p is enriched in Hypo-sEV, and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105, which attenuates osteolysis. Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression. Hypoxia promotes the release of sEV from DPSCs. Hypoxia-induced DPSC-sEV (Hypo-sEV) show increased potential to inhibit inflammatory osteolysis. The miR-210-3p enriched in Hypo-sEV contributes to therapeutic effects of Hypo-sEV. MiR-210-3p concurrently induces M2 macrophage generation and inhibits osteoclastogenesis by targeting NF-κB1. Hypoxia-induced DPSC-sEV represent a promising therapy for inflammatory osteolysis.
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影响因子：
16
作者：
Lee KS;Lee J;Kim HK;Yeom SH;Woo CH;Jung YJ;Yun YE;Park SY;Han J;Kim E;Sul JH;Jung JM;Park JH;Choi JS;Cho YW;Jo DG
通讯作者：
Jo DG
DOI：
10.4161/cc.9.6.11006
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chan SY;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
8.1
作者：
Imanishi Y;Hata M;Matsukawa R;Aoyagi A;Omi M;Mizutani M;Naruse K;Ozawa S;Honda M;Matsubara T;Takebe J
通讯作者：
Takebe J
影响因子：
9.2
作者：
Kwak, Sung Chul;Baek, Jong Min;Kim, Ju-Young
通讯作者：
Kim, Ju-Young
影响因子：
4.4
作者：
Ji, Lujun;Bao, Liuliu;Feng, Xingmei
通讯作者：
Feng, Xingmei