High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

Abstract

BackgroundMechanical overloading can lead to disc degeneration. Nucleus pulposus (NP) cell senescence is aggravated within the degenerated disc. This study was designed to investigate the effects of high compression on NP cell senescence and the underlying molecular mechanism of this process.MethodsRat NP cells seeded in decalcified bone matrix were subjected to non-compression (control) or compression (2% or 20% deformation, 1.0 Hz, 6 hours/day). The reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580 were used to investigate the roles of the ROS and p38 MAPK pathway under high-magnitude compression. Additionally, we studied the effects of compression (0.1 or 1.3 MPa, 1.0 Hz, 6 hours/day) in a rat disc organ culture.ResultsBoth in scaffold and organ cultures, high-magnitude compression (20% deformation or 1.3 MPa) increased senescence-associated β-galactosidase (SA-β-Gal) activity, senescence marker (p16 and p53) expression, G1 cell cycle arrest, and ROS generation, and decreased cell proliferation, telomerase activity and matrix (aggrecan and collagen II) synthesis. Further analysis of the 20% deformation group showed that NAC inhibited NP cell senescence but had no obvious effect on phospho-p38 MAPK expression and that SB203580 significantly attenuated ROS generation and NP cell senescence.ConclusionsHigh-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1384-z) contains supplementary material, which is available to authorized users.

P38-Mediated Cellular Senescence in Conjunctivochalasis Fibroblasts

“…34 High-magnitude compression accelerated cellular senescence by the p38 MAPK-ROS pathway in the nucleus pulposus. 36 However, views on the relation of p38 MAPK and ROS are not unanimous. Probin et al 37 demonstrated that ROS acted as an upstream of p38 MAPK pathway in busulfan-induced cellular senescence of normal human diploid WI38 fibroblasts.…”

LncRNA H19 targets miR‐22 to modulate H2O2‐induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling

“…Human NPCs were isolated using a method reported earlier by Risbud et al 42 43,44 and/or N-acetyl-l-cysteine (NAC, 5 mM), 16 a ROS scavenger, for 2 h.…”

Nucleus pulposus cell apoptosis is attenuated by CDMP-2 through regulating oxidative damage under the hyperosmotic environment

“…Increasing studies have indicated that initiation and aggravation of disc degeneration are closely associated with oxidative stress damage [ 44–46 ]. As an important initiator of disc degeneration, mechanical load also increases generation of the intracellular ROS, and causes oxidative damage [ 47–51 ]. As the secondary event of mechanical compression, the hyperosmolarity environment also causes oxidative damage in corneal epithelial cells [ 52 ].…”