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Mechanical Stretch Induces Annulus Fibrosus Cell Senescence through Activation of the RhoA/ROCK Pathway.
- Source :
-
BioMed research international [Biomed Res Int] 2021 Nov 19; Vol. 2021, pp. 5321121. Date of Electronic Publication: 2021 Nov 19 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Background: Intervertebral disc is responsible for absorbing and transmitting mechanical compression. Under physiological conditions, the peripheral annulus fibrosus (AF) cells are subjected to different magnitudes of transverse mechanical stretch depending on the swelling of the central nucleus pulposus tissue. However, the biological behavior of AF cells under mechanical stretch is not well studied.<br />Objective: This study was performed to study the effects of mechanical tension on AF cell senescence and the potential signaling transduction pathway.<br />Methods: Rat AF cells were made to experience different magnitudes of mechanical stretch (2% elongation and 20% elongation for 4 hours every day at 1 Hz) in a 10-day experiment period. The inhibitor RKI-1447 of the Rho-associated coiled-coil-containing protein kinases (ROCK) was added along with culture medium to investigate its role. Cell proliferation, cell cycle, telomerase activity, and expression of senescence markers (p16 and p53) were analyzed.<br />Results: We found that 20% elongation significantly decreased cell proliferation, promoted G0/G1 cell cycle arrest, decreased telomerase activity, and upregulated mRNA/protein expression of p16 and p53. Moreover, the inhibitor RKI-1447 partly resisted effects of 20% elongation on these parameters of cell senescence.<br />Conclusion: High mechanical stretch obviously induces AF cell senescence through the RhoA/ROCK pathway. This study provides us a deeper understanding on the AF cell's behavior under mechanical stretch.<br />Competing Interests: The authors declared no conflicts of interest.<br /> (Copyright © 2021 Li Ning et al.)
- Subjects :
- Animals
Annulus Fibrosus drug effects
Cell Proliferation
Cells, Cultured
Cellular Senescence physiology
G1 Phase Cell Cycle Checkpoints
Intervertebral Disc Degeneration etiology
Intervertebral Disc Degeneration pathology
Intervertebral Disc Degeneration physiopathology
Protein Kinase Inhibitors pharmacology
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Stress, Mechanical
Telomerase metabolism
Thiazoles pharmacology
Urea analogs & derivatives
Urea pharmacology
rho-Associated Kinases antagonists & inhibitors
Annulus Fibrosus cytology
Annulus Fibrosus physiology
rho GTP-Binding Proteins metabolism
rho-Associated Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2021
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 34840974
- Full Text :
- https://doi.org/10.1155/2021/5321121