Cyclic mechanical pressure reinforces DNA harm and prompts the p53-p21-Rb pathway to induce untimely senescence of nucleus pulposus cells.
Int J Mol Med. 2018 Jun;41(6):3316-3326
Authors: Feng C, Yang M, Zhang Y, Lan M, Huang B, Liu H, Zhou Y
Intervertebral disc (IVD) degeneration (IDD) is a well known contributor to low again ache. Mechanical stress is a vital etiological issue of IDD. In the course of the means of IDD, a vicious circle is shaped between irregular mechanical stress and the harm of disc construction and performance. Notably, the pathological means of IDD is mediated by the phenotypic shift of IVD cells from an extracellular matrix anabolic phenotype to a catabolic and pro-inflammatory phenotype. Due to this fact, the results of mechanical stress on the initiation and development of IDD rely upon the mechanobiology of IVD cells. Just lately, disc cell senescence was recognized as a brand new hallmark of IDD. Nonetheless, the senescent response of disc cells to mechanical stress stays unknown. On this research, we discovered that extended publicity of cyclic mechanical pressure (CMT) with unphysiological magnitude generated by the Flexercell pressure system markedly induced untimely senescence of nucleus pulposus (NP) cells. CMT augmented the DNA harm of NP cells, however didn’t have an effect on the redox homeostasis of NP cells. Furthermore, the p53-p21-retinoblastoma protein (Rb) pathway was activated by CMT to mediate the CMT-induced untimely senescence of NP cells. The findings are helpful to understanding the mechanism of disc cell senescence and the mechanobiology of disc cells additional. It means that extended irregular mechanical stress accelerates the institution and development of disc cell senescence and consequently impairs the structural and practical homeostasis of IVDs to trigger IDD. Stopping the pro-senescent impact of mechanical stress on IVD cells is a promising strategy to delay the method of IDD.
PMID: 29512682 [PubMed – indexed for MEDLINE]