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.
Highlights
Mechanical overloading can lead to disc degeneration
Experiments performed on the nucleus pulposus (NP) cell scaffold culture High-magnitude compression induced reactive oxygen species (ROS) generation in NP cells Results showed that 20% deformation compression significantly increased ROS generation compared with 2% deformation compression
The results showed that the percentage of dying NP cells in the 20% deformation compression group (22.17%) increased compared with the 2% deformation compression group (4.31%) and the control group (3.55%)
Summary
Mechanical overloading can lead to disc degeneration. Nucleus pulposus (NP) cell senescence is aggravated within the degenerated disc. Cellular senescence accumulation within the disc tissue is common during disc ageing and degeneration [1,2,3]. Notwithstanding this important discovery, the potential mechanism of disc cellular senescence is not fully understood. The senescence-related markers do not show an age-related upregulation in degenerative discs [6, 7, 9]. These findings indirectly suggest that there may be some other factors that can aggravate cellular senescence during disc degeneration and disc ageing apart from the natural ageing process
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