1. Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway.
- Author
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Ge J, Cheng X, Yuan C, Qian J, Wu C, Cao C, Yang H, Zhou F, and Zou J
- Subjects
- Aggrecans genetics, Aggrecans metabolism, Animals, Blotting, Western, Chromatin Immunoprecipitation, Humans, Intervertebral Disc Degeneration genetics, Intervertebral Disc Degeneration pathology, MAP Kinase Signaling System genetics, MAP Kinase Signaling System physiology, Magnetic Resonance Imaging, Nucleus Pulposus pathology, Polymerase Chain Reaction, Protein Binding, Proto-Oncogene Proteins c-mdm2 genetics, Proto-Oncogene Proteins c-mdm2 metabolism, Rabbits, Signal Transduction genetics, Signal Transduction physiology, Syndecan-4 genetics, Syndecan-4 metabolism, Intervertebral Disc Degeneration metabolism, Nucleus Pulposus metabolism, Syndecan-4 physiology
- Abstract
Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo . We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2020
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