1. Academic Validation
  2. Tension induces intervertebral disc degeneration via endoplasmic reticulum stress-mediated autophagy

Tension induces intervertebral disc degeneration via endoplasmic reticulum stress-mediated autophagy

  • Biosci Rep. 2019 Aug 7;39(8):BSR20190578. doi: 10.1042/BSR20190578.
Jiangwei Chen 1 Zunwen Lin 1 Kui Deng 1 Bin Shao 2 Dong Yang 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 2 Department of Orthopedics, Jingdezhen First People's Hospital, Jingdezhen, China.
  • 3 Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, China dr_yangdong@126.com.
Abstract

Background: Intervertebral disc degeneration is a common degenerative disease. The present study aimed to explore the role and mechanism of tension-induced endoplasmic reticulum stress in intervertebral disc degeneration.

Methods: Intervertebral disc degeneration models of SD rat were analyzed for Apoptosis, the expression of Poly(ADP-ribose) polymerase (PARP), Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP using immunohistochemistry, qPCR and Western blot analysis. Annulus fibrosus cells of intervertebral disc were isolated, subjected to cyclic deformation stress and analyzed for ROS and Apoptosis, lysosome activity and expression of genes. The cells were knockdown with siRNA or treated with endoplasmic reticulum stress inhibitor 4-PBA and assayed for ROS, Apoptosis, lysosome activity and gene expression.

Results: Compared with the controls, intervertebral disc degeneration was observed through X-rays examinations and HS staining. Apoptosis and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly increased in the intervertebral disc tissue of the models. In mechanic mimic experiments, the primary annulus fibrosus cells were subjected to 18% cyclic deformation, ROS and Apoptosis as well as the activity of lysosome were increased. Similarly, the expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP was also increased significantly after deformation treatment. On other hand, when the cells were treated with 9 mM 4-PBA and/or CHOP-siRNA4, the Apoptosis rate, ROS level, lysosome activity and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly reduced.

Conclusions: Autophagy reaction mediated by endoplasmic reticulum stress plays important rale in tension-induced intervertebral disc degeneration. Intervertebral disc degeneration likely results from interactions between Autophagy, Apoptosis and reticulum stress, and is ROS-dependent.

Keywords

autophagy; cyclic deformation; endoplasmic reticulum stress; intervertebral disc degeneration.

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