期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 44, 期 1, 页码 229-239出版社
KARGER
DOI: 10.1159/000484649
关键词
Compression; Apoptosis; Nucleus pulposus cell; PI3K/Akt; N-cadherin
资金
- National Natural Science Foundation of China [81601932, 81027005, 81272029]
- Science and Technology Achievement Transformation Fund of Third Military Medical University [2011XZH006]
Background/Aims: Mechanical overloading-induced nucleus pulposus (NP) apoptosis plays an important role in the pathogenesis of intervertebral disc degeneration. N-cadherin (N-CDH)-mediated signaling preserves normal NP cell phenotype. This study aims to investigate the effects of N-CDH on NP cell apoptosis under high-magnitude compression and the underlying mechanism behind this process. Methods: Rat NP cells seeded on scaffold were perfusion-cultured using a self-developed perfusion bioreactor for 5 days and experienced different magnitudes (2% and 20% compressive deformation, respectively) of compression at a frequency of 1.0 Hz for 4 hours once per day. The un-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression and inhibitor LY294002 were used to further investigate the role of N-CDH and PI3K/Akt pathway under high-magnitude compression, respectively. NP cell apoptosis was evaluated by caspase-3 activity measured using a commercial kit, flow cytometry, and expression of apoptosis-related molecules analyzed by real-time PCR and western blotting assays. Results: High-magnitude compression significantly increased apoptotic NP cells, caspase-3 activity and expression of pro-apoptotic molecules (Bax and caspase-3/cleaved caspase-3), but decreased expression of anti-apoptotic molecule (Bcl-2). High-magnitude compression decreased expression of N-CDH, p-Akt and p-GSK-3 beta. However, N-CDH overexpression attenuated NP cell apoptosis and increased expression of p-Akt and p-GSK-3 beta under high-magnitude compression. Further analysis showed that inhibition of the PI3K/Akt pathway suppressed NP cell apoptosis and decreased expression of p-GSK-3 beta, but had no significant effects on N-CDH expression under high-magnitude compression. Conclusion: N-CDH can attenuate NP cell apoptosis through activating the PI3K/Akt-GSK-3 beta signaling under high-magnitude compression. (c) 2017 The Author(s) Published by S. Karger AG, Basel
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