Mesenchymal stem cell (MSCs)‐based therapies have shown a promised result for intervertebral disc degeneration (IVDD) treatment. However, its molecular mechanisms remain unclear. Exosomes involve cell‐cell communication via transference of its contents among different cells, and the present potential effect on cell death regulation. This study aimed to investigate the role of MSCs‐derived exosomes on IVDD formation. Here, we first found the NLRP3‐mediated nucleus pulposus cell (NP cell) pyroptosis was activated in the IVDD mice model and lipopolysaccharide (LPS)‐induced model. However, MSCs treatment could inhibit NP cell pyroptosis in vitro. We then isolated MSCs‐derived exosomes by differential centrifugation and identified the characteristics. Secondly, we investigated the function of MSCs‐derived exosomes on LPS‐induced NP cell pyroptosis. Finally, we presented evidence that MSCs‐derived exosomal miR‐410 was a crucial regulator of pyroptosis. Results showed that MSCs‐derived exosomes play an anti‐pyroptosis role by suppressing the NLRP3 pathway. Moreover, it suggested that this effect was attributed to miR‐410, which was derived from MSCs‐exosomes and could directly bind to NLRP3mRNA. In conclusion, for the first time, we demonstrated that MSCs‐exosome treatment may inhibit pyroptosis and could be a promising therapeutic strategy for IVDD.

中文翻译：

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间充质干细胞来源的外来体通过抑制焦磷酸化来改善椎间盘退变。

基于间充质干细胞（MSCs）的治疗方法已显示出椎间盘退变（IVDD）治疗的有希望的结果。但是，其分子机制仍不清楚。外泌体通过其内容在不同细胞之间的转移而涉及细胞间的通讯，以及目前对细胞死亡调控的潜在影响。这项研究旨在调查MSCs外来体在IVDD形成中的作用。在这里，我们首先发现在IVDD小鼠模型和脂多糖（LPS）诱导的模型中激活了NLRP3介导的髓核细胞（NP细胞）凋亡。然而，MSCs处理可以在体外抑制NP细胞的凋亡。然后，我们通过差速离心分离了MSCs衍生的外泌体，并鉴定了特征。其次，我们研究了MSCs外来体对LPS诱导的NP细胞凋亡的作用。最后，我们提供了证据表明，MSCs的外泌体miR-410是细胞凋亡的关键调节剂。结果显示，MSCs的外来体通过抑制NLRP3途径发挥抗化脓作用。此外，它暗示了这种作用归因于miR-410，它源自MSCs外泌体，可以直接与NLRP3mRNA结合。总之，我们首次证明了MSCs外泌体治疗可能抑制细胞凋亡，并可能成为IVDD的有前途的治疗策略。