The online version of this article (doi:10.1186/s13075-017-1384-z) contains supplementary material, which is available to authorized users.
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.
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.
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.
High-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.
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)
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)
Tomiyama T, Fukuda K, Yamazaki K, Hashimoto K, Ueda H, Mori S, Hamanishi C. Cyclic compression loaded on cartilage explants enhances the production of reactive oxygen species. J Rheumatol. 2007;34(3):556–62. PubMed
Ariga K, Yonenobu K, Nakase T, Hosono N, Okuda S, Meng W, Tamura Y, Yoshikawa H. Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study. Spine. 2003;28(14):1528–33. PubMed
Li P, Gan Y, Xu Y, Li S, Song L, Li S, Li H, Zhou Q. Osmolarity affects matrix synthesis in the nucleus pulposus associated with the involvement of MAPK pathways: A study of ex vivo disc organ culture system. J Orthop Res. 2016;34(6):1092–100.
Li P, Gan Y, Xu Y, Song L, Wang H, Zhang C, Wang L, Zhao C, Luo L, Zhou Q. Matrix homeostasis within the immature annulus fibrosus depends on the frequency of dynamic compression: a study based on the self-developed mechanically active bioreactor. Biomech Model Mechanobiol. 2017;16(2):385–94. CrossRefPubMed
Lander HM. An essential role for free radicals and derived species in signal transduction. FASEB J. 1997;11(2):118–24. PubMed
Li P, Zhang R, Xu Y, Song L, Zhou Q. Role of p38-MAPK pathway in the effects of high -magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture. Biosci Rep. 2017. doi: 10.1042/BSR20170718. [Epub ahead of print].
- High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
- BioMed Central
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