Intercellular mitochondrial transfer alleviates pyroptosis in dental pulp damage.
Intercellular mitochondrial transfer alleviates pyroptosis in dental pulp damage.
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细胞间线粒体转移可减轻牙髓损伤后的热下垂。
DOI：
10.1111/cpr.13442
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发表时间：
2023-09
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体转移正在成为一种有前途的组织修复治疗策略，但它是否能预防牙髓炎仍不清楚。在这里，我们发现，在牙髓炎组织中，特别是在成牙本质细胞层中，存在过度活化的核苷酸结合结构域和富含亮氨酸重复序列蛋白3（NLRP 3）炎性小体，并伴有细胞死亡，线粒体氧化应激（OS）参与驱动这种NLRP 3炎性小体诱导的病理。使用骨髓间充质干细胞（BMSCs）作为线粒体供体细胞，我们证明BMSCs可以通过隧道纳米管（TNT）将其线粒体捐赠给成牙本质细胞，从而减少成牙本质细胞中的线粒体OS和随后的NLRP 3炎性小体诱导的焦亡。BMSCs的这些保护作用主要被线粒体功能或TNT形成的抑制剂阻断。从作用机制上看，脓毒性成牙本质细胞分泌的TNF-α通过旁分泌途径激活BMSCs中的NF-κB信号，从而促进BMSCs中TNT的形成，提高线粒体转运效率。抑制NF-κB信号和TNF-α分泌可抑制BMSCs的线粒体捐献能力和TNT形成。总的来说，这些发现表明TNT介导的线粒体转移是BMSCs在应激条件下的潜在保护机制，这表明线粒体转移用于牙髓修复的新治疗策略。LPS + ATP诱导mDPC 6 T细胞中线粒体功能障碍和随后的NLRP 3活化和焦亡。在mBMSC与mDPC 6 T细胞共培养期间，mDPC 6 T细胞分泌TNF-α作为促进TNT介导的线粒体转移的主要因素，并证实TNT形成是NF-κB依赖性的。重要的是，来自mBMSC的线粒体被选择性地转移到受损的mDPC 6 T细胞，这保护mDPC 6 T细胞免受损伤。
Mitochondrial transfer is emerging as a promising therapeutic strategy for tissue repair, but whether it protects against pulpitis remains unclear. Here, we show that hyperactivated nucleotide‐binding domain and leucine‐rich repeat protein3 (NLRP3) inflammasomes with pyroptotic cell death was present in pulpitis tissues, especially in the odontoblast layer, and mitochondrial oxidative stress (OS) was involved in driving this NLRP3 inflammasome‐induced pathology. Using bone marrow mesenchymal stem cells (BMSCs) as mitochondrial donor cells, we demonstrated that BMSCs could donate their mitochondria to odontoblasts via tunnelling nanotubes (TNTs) and, thus, reduce mitochondrial OS and the consequent NLRP3 inflammasome‐induced pyroptosis in odontoblasts. These protective effects of BMSCs were mostly blocked by inhibitors of the mitochondrial function or TNT formation. In terms of the mechanism of action, TNF‐α secreted from pyroptotic odontoblasts activates NF‐κB signalling in BMSCs via the paracrine pathway, thereby promoting the TNT formation in BMSCs and enhancing mitochondrial transfer efficiency. Inhibitions of NF‐κB signalling and TNF‐α secretion in BMSCs suppressed their mitochondrial donation capacity and TNT formation. Collectively, these findings demonstrated that TNT‐mediated mitochondrial transfer is a potential protective mechanism of BMSCs under stress conditions, suggesting a new therapeutic strategy of mitochondrial transfer for dental pulp repair. LPS + ATP induced mitochondrial dysfunction and subsequent NLRP3 activation and pyroptosis in mDPC6T cells. mDPC6T cells‐secreted TNF‐α as a major factor in promoting TNT‐mediated mitochondrial transfer during the coculture of mBMSCs with mDPC6T cells and confirmed that the TNT formation was NF‐κB‐dependent. Importantly, mitochondria from mBMSCs are selectively transferred to injured mDPC6T cells, which protects mDPC6T cells from injury.
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影响因子：
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影响因子：
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Forte D;García-Fernández M;Sánchez-Aguilera A;Stavropoulou V;Fielding C;Martín-Pérez D;López JA;Costa ASH;Tronci L;Nikitopoulou E;Barber M;Gallipoli P;Marando L;Fernández de Castillejo CL;Tzankov A;Dietmann S;Cavo M;Catani L;Curti A;Vázquez J;Frezza C;Huntly BJ;Schwaller J;Méndez-Ferrer S
通讯作者：
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DOI：
10.1073/pnas.2000915118
发表时间：
2021-03-09
影响因子：
11.1
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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