Affiliation:
1. Spine Research Center of Wannan Medical College, Department of Spine Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, P.R. China
Abstract
Study Design Basic Research. Objective Intervertebral disc degeneration (IVDD) is caused by the cartilage endplate (CEP). Cartilage endplate stem cell (CESC) is involved in the recovery of CEP degeneration. Tension load (TL) contributes a lot to the initiation and progression of IVDD. This study aims to investigate the regulatory mechanism of the Mitogen-activated protein kinases/Mammalian target of rapamycin (MAPK/mTOR) pathway during TL-induced CESC degeneration. Methods CESCs were isolated from New Zealand big-eared white female rabbits (6 months old). FX-4000T cell stress loading system was applied to establish a TL-induced degeneration model of CESCs. Western blotting was used to detect the level of mTOR pathway-related proteins and autophagy markers LC3-Ⅱ, Beclin-1, and p62 in degenerative CESCs. The expression of MAPK pathway-related proteins JNK and extracellular signal-regulated kinases (ERK) in degenerated CESCs was inhibited by cell transfection to explore whether JNK and ERK play a regulatory role in TL-induced autophagy in CESCs. Results In the CESC degeneration model, the mTOR pathway was activated. After inhibition of mTOR, the autophagy level of CESCs was increased, and the degeneration of CESCs was alleviated. The MAPK pathway was also activated in the CESC degeneration model. Inhibition of JNK expression may alleviate TL-induced CEP degeneration by inhibiting Raptor phosphorylation and activating autophagy. Inhibition of ERK expression may alleviate TL-induced CEP degeneration by inhibiting mTOR phosphorylation and activating autophagy. Conclusion Inhibition of JNK and ERK in the MAPK signaling family alleviated TL-induced CESC degeneration by inhibiting the phosphorylation of Raptor and mTOR in the mTOR pathway.
Funder
National Natural Science Foundation of China
“Panfeng” Innovation Team Project and “Peak” Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College
Subject
Neurology (clinical),Orthopedics and Sports Medicine,Surgery
Cited by
4 articles.
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