Department of Spine Center, Zhongda Hospital, Medical School, Southeast University, China.
Department of gynaecology and obstetrics, The Affiliated Jiangning Hospital of Nanjing Medical University, China.
Exp Gerontol. 2022 Jul;164:111829. doi: 10.1016/j.exger.2022.111829. Epub 2022 May 13.
Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-α is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-α-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-α-induced biological changes of BMSCs. Here, we found that TNF-α caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-α irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-α, which could be a crucial therapeutic target in the future.
骨髓间充质干细胞（BMSCs）已被研究作为细胞疗法用于治疗椎间盘退变。然而，移植的 BMSCs 容易受到损伤。TNF-α 被报道广泛促进退变过程。然而，BMSCs 衰老与 TNF-α 诱导的应激之间的关系尚未阐明。先前的研究表明，线粒体自噬是维持细胞内稳态的关键因素。因此，我们试图阐明线粒体自噬在 TNF-α诱导的 BMSCs 生物学变化中的作用和机制。在这里，我们发现 TNF-α 在早期引起短暂的衰老损伤。同时，Parkin 介导的线粒体自噬被启动，并通过维持线粒体稳态来减轻损伤。通过敲低 Parkin 抑制线粒体自噬后，TNF-α 不可逆地引起细胞衰老。这些结果表明，Parkin 介导的线粒体自噬在 BMSCs 对 TNF-α 的反应中发挥保护作用，这可能是未来的一个重要治疗靶点。
