Feng Chencheng, Liu Huan, Yang Minghui, Zhang Yang, Huang Bo, Zhou Yue
a Department of Orthopedics , Xinqiao Hospital, Third Military Medical University , Chongqing , People's Republic of China.
Cell Cycle. 2016 Jul 2;15(13):1674-84. doi: 10.1080/15384101.2016.1152433. Epub 2016 May 18.
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.
衰老的椎间盘细胞在退变的椎间盘（IVD）中积累，提示细胞衰老在椎间盘退变（IDD）发病机制中起有害作用。椎间盘细胞衰老减少了IVD中功能细胞的数量。此外，衰老的椎间盘细胞被认为通过其异常的旁分泌作用加速IDD进程，衰老细胞导致邻近细胞衰老，并增强IVD中的基质分解代谢和炎症。因此，抗衰已被提出作为IDD的一种新型治疗靶点。然而，抗衰治疗的发展基于我们对椎间盘细胞衰老分子机制的理解。在本综述中，我们聚焦于椎间盘细胞衰老的分子机制，包括其原因和各种分子途径。我们发现，在IDD过程中，与年龄相关的损伤以及退行性外部刺激激活了p53-p21-Rb和p16-Rb两条途径，从而诱导椎间盘细胞衰老。同时，椎间盘细胞衰老受多种信号通路调控，提示椎间盘细胞衰老存在复杂的调控网络。更好地理解椎间盘细胞衰老机制有助于开发基于抗衰的IDD治疗方法。
