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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Arthritis Research & Therapy 1/2017

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

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2017
Autoren:
Pei Li, Gang Hou, Ruijie Zhang, Yibo Gan, Yuan Xu, Lei Song, Qiang Zhou
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13075-017-1384-z) contains supplementary material, which is available to authorized users.

Abstract

Background

Mechanical 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.

Methods

Rat 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.

Results

Both 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.

Conclusions

High-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.
Zusatzmaterial
Additional file 1: Figure S1. Identification of nucleus pulposus (NP) cells. (A) NP cells under a light microscope. NP cells exhibited short shuttle-like, round or polygon shapes. Magnification: ×200. (B) Analysis of gene expression of NP cell-specific markers (CAXII, Keratin-19, FOXF1, and PAX1). (PDF 476 kb)
13075_2017_1384_MOESM1_ESM.pdf
Additional file 2: Figure S2. Analysis of the percentage of dying nucleus pulposus (NP) cells in each group. The flow cytometry assay 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%). However, treatment with the ROS scavenger NAC and the p38 MAPK inhibitor SB203580 decreased 20% deformation compression-induced NP cell apoptosis (from 22.17 to 16.83% and from 22.17 to 11.65%, respectively). (PDF 353 kb)
13075_2017_1384_MOESM2_ESM.pdf
Literatur
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