Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways.

The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD.

退化椎间盘（IVD）中衰老椎间盘细胞的积累表明细胞衰老在椎间盘变性（IDD）的发病机理中的有害作用。椎间盘细胞衰老减少了IVD中功能细胞的数量。此外，衰老的椎间盘细胞应该通过其异常的旁分泌作用加速IDD的过程，衰老细胞会导致邻近细胞的衰老并增强IVD中基质分解代谢和炎症。因此，已提出抗染色为IDD的新型治疗靶标。然而，抗染色疗法的发展是基于我们对椎间盘细胞衰老的分子机制的理解。在这篇综述中，我们专注于椎间盘细胞衰老的分子机制，包括原因和各种分子途径。我们发现，在IDD的过程中，与年龄相关的损害以及退化性外部刺激激活了p53-P21-RB和P16-RB途径，以诱导椎间盘衰老。同时，椎间盘细胞衰老受多种信号通路调节，表明复杂的调节盘细胞衰老网络。为了了解椎间盘细胞衰老的机制，可以更好地有助于开发IDD的基于抗染色的疗法。